Trial Outcomes & Findings for Study In Postmenopausal Women With Type 2 Diabetes Looking At Approved Diabetes Drugs And How They Affect Bone Health (NCT NCT00679939)

Results Overview

FN BMD (measured in grams per centimeters squared \[g/cm\^2\]) was measured by DXA. Bone mineral density is calculated as the mineral content of a bone divided by the area of the bone. DXA is the principal technique used for measuring BMD. Percent change from Baseline at Week 52 was calculated as (BMD at Week 52 minus BMD at Baseline)/BMD at Baseline x 100% and was assessed by analysis of covariance (ANCOVA) with terms for treatment, baseline value, prior therapy, and region. Change in FN BMD at Week 52 was only analyzed within the Rosiglitazone arm.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

226 participants

Primary outcome timeframe

Baseline and Week 52

Results posted on

2018-04-18

Participant Flow

Participant milestones

Participant milestones
Measure	Rosiglitazone in DB Period; Metformin in OL Period Rosiglitazone (RSG) initiated at a total daily dose of 4 milligrams (mg) in the 52-week DB Period. RSG could be uptitrated to a total daily dose of 8 mg at Week 4. At Week 52, all participants were switched to open-label (OL) Metformin (MET) therapy for 24 weeks during the follow-up phase; all participants were force-titrated from 1000 mg/day to 2000 mg/day over a 4-week period. However, participants could be down-titrated to alleviate any MET-related tolerability issues.	Metformin in DB Period; Metformin in OL Period Metformin (MET) initiated at a total daily dose of 1000 mg in the 52-week DB Period. MET could be uptitrated to 1500 mg/day at Week 2 and to 2000 mg/day at Week 4. At Week 52, all participants were switched to open-label MET therapy for 24 weeks during the follow-up phase; all participants were force-titrated from 1000 mg/day to 2000 mg/day over a 4-week period. However, participants could be down-titrated to alleviate any MET-related tolerability issues.
52-Week Double-Blind (DB) Period STARTED	114	112
52-Week Double-Blind (DB) Period COMPLETED	77	85
52-Week Double-Blind (DB) Period NOT COMPLETED	37	27
24-Week Open-Label (OL) Period STARTED	76	84
24-Week Open-Label (OL) Period COMPLETED	69	80
24-Week Open-Label (OL) Period NOT COMPLETED	7	4

Reasons for withdrawal

Reasons for withdrawal
Measure	Rosiglitazone in DB Period; Metformin in OL Period Rosiglitazone (RSG) initiated at a total daily dose of 4 milligrams (mg) in the 52-week DB Period. RSG could be uptitrated to a total daily dose of 8 mg at Week 4. At Week 52, all participants were switched to open-label (OL) Metformin (MET) therapy for 24 weeks during the follow-up phase; all participants were force-titrated from 1000 mg/day to 2000 mg/day over a 4-week period. However, participants could be down-titrated to alleviate any MET-related tolerability issues.	Metformin in DB Period; Metformin in OL Period Metformin (MET) initiated at a total daily dose of 1000 mg in the 52-week DB Period. MET could be uptitrated to 1500 mg/day at Week 2 and to 2000 mg/day at Week 4. At Week 52, all participants were switched to open-label MET therapy for 24 weeks during the follow-up phase; all participants were force-titrated from 1000 mg/day to 2000 mg/day over a 4-week period. However, participants could be down-titrated to alleviate any MET-related tolerability issues.
52-Week Double-Blind (DB) Period Withdrew Consent	17	13
52-Week Double-Blind (DB) Period Adverse Event	14	12
52-Week Double-Blind (DB) Period Investigator Discretion	5	0
52-Week Double-Blind (DB) Period Protocol Violation	1	0
52-Week Double-Blind (DB) Period Lost to Follow-up	0	2
24-Week Open-Label (OL) Period Adverse Event	0	1
24-Week Open-Label (OL) Period Protocol Violation	1	1
24-Week Open-Label (OL) Period Met Stopping Criteria	3	1
24-Week Open-Label (OL) Period Physician Decision	1	0
24-Week Open-Label (OL) Period Withdrawal by Subject	2	1

Baseline Characteristics

Study In Postmenopausal Women With Type 2 Diabetes Looking At Approved Diabetes Drugs And How They Affect Bone Health

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Rosiglitazone in DB Period; Metformin in OL Period n=114 Participants Rosiglitazone (RSG) initiated at a total daily dose of 4 milligrams (mg) in the 52-week DB Period. RSG could be uptitrated to a total daily dose of 8 mg at Week 4. At Week 52, all participants were switched to open-label (OL) Metformin (MET) therapy for 24 weeks during the follow-up phase; all participants were force-titrated from 1000 mg/day to 2000 mg/day over a 4-week period. However, participants could be down-titrated to alleviate any MET-related tolerability issues.	Metformin in DB Period; Metformin in OL Period n=111 Participants Metformin (MET) initiated at a total daily dose of 1000 mg in the 52-week DB Period. MET could be uptitrated to 1500 mg/day at Week 2 and to 2000 mg/day at Week 4. At Week 52, all participants were switched to open-label MET therapy for 24 weeks during the follow-up phase; all participants were force-titrated from 1000 mg/day to 2000 mg/day over a 4-week period. However, participants could be down-titrated to alleviate any MET-related tolerability issues.	Total n=225 Participants Total of all reporting groups
Age, Continuous	63.6 Years STANDARD_DEVIATION 6.61 • n=99 Participants	64.0 Years STANDARD_DEVIATION 6.46 • n=107 Participants	63.8 Years STANDARD_DEVIATION 6.52 • n=206 Participants
Sex: Female, Male Female	114 Participants n=99 Participants	111 Participants n=107 Participants	225 Participants n=206 Participants
Sex: Female, Male Male	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Race/Ethnicity, Customized White - White/Caucasian/European	82 participants n=99 Participants	78 participants n=107 Participants	160 participants n=206 Participants
Race/Ethnicity, Customized African American/African	2 participants n=99 Participants	8 participants n=107 Participants	10 participants n=206 Participants
Race/Ethnicity, Customized American Indian or Alaskan Native	6 participants n=99 Participants	5 participants n=107 Participants	11 participants n=206 Participants
Race/Ethnicity, Customized Asian - Central/South Asian	13 participants n=99 Participants	10 participants n=107 Participants	23 participants n=206 Participants
Race/Ethnicity, Customized South East Asian	4 participants n=99 Participants	6 participants n=107 Participants	10 participants n=206 Participants
Race/Ethnicity, Customized Mixed Race	3 participants n=99 Participants	2 participants n=107 Participants	5 participants n=206 Participants
Race/Ethnicity, Customized East Asia	4 participants n=99 Participants	2 participants n=107 Participants	6 participants n=206 Participants

PRIMARY outcome

Timeframe: Baseline and Week 52

Population: Safety Population. Only evaluable participants with a value at baseline and at Week 52 for the parameter of interest were analyzed. Only participants with Baseline DXA and Week 52 DXA measurements performed on or prior to initiating open-label MET are included in this primary analysis.

FN BMD (measured in grams per centimeters squared \[g/cm\^2\]) was measured by DXA. Bone mineral density is calculated as the mineral content of a bone divided by the area of the bone. DXA is the principal technique used for measuring BMD. Percent change from Baseline at Week 52 was calculated as (BMD at Week 52 minus BMD at Baseline)/BMD at Baseline x 100% and was assessed by analysis of covariance (ANCOVA) with terms for treatment, baseline value, prior therapy, and region. Change in FN BMD at Week 52 was only analyzed within the Rosiglitazone arm.

Outcome measures

Outcome measures
Measure	Rosiglitazone in DB Period; Metformin in OL Period n=52 Participants Rosiglitazone (RSG) initiated at a total daily dose of 4 milligrams (mg) in the 52-week DB Period. RSG could be uptitrated to a total daily dose of 8 mg at Week 4. At Week 52, all participants were switched to open-label (OL) Metformin (MET) therapy for 24 weeks during the follow-up phase; all participants were force-titrated from 1000 mg/day to 2000 mg/day over a 4-week period. However, participants could be down-titrated to alleviate any MET-related tolerability issues.	Metformin in DB Period; Metformin in OL Period Metformin (MET) initiated at a total daily dose of 1000 mg in the 52-week DB Period. MET could be uptitrated to 1500 mg/day at Week 2 and to 2000 mg/day at Week 4. At Week 52, all participants were switched to open-label MET therapy for 24 weeks during the follow-up phase; all participants were force-titrated from 1000 mg/day to 2000 mg/day over a 4-week period. However, participants could be down-titrated to alleviate any MET-related tolerability issues.
Adjusted Percent Change From Baseline in Femoral Neck (FN) Bone Mineral Density (BMD) Via Dual-energy X-ray Absorptiometry (DXA) at Week 52	-1.24 percent change Standard Error 0.619	—

PRIMARY outcome

Timeframe: Baseline and Week 76+10 days

Population: Safety Population. Only evaluable participants with a value at baseline and at Week 76 performed up to 10 days after stopping OL MET for the parameter of interest were analyzed.

FN BMD (measured in grams per centimeters squared \[g/cm\^2\]) was measured by DXA. Bone mineral density is calculated as the mineral content of a bone divided by the area of the bone. DXA is the principal technique used for measuring BMD. Percent change from Baseline at Week 76+10 days was calculated as (BMD at Week 76+10 days minus BMD at Baseline)/BMD at Baseline x 100% and was assessed by analysis of covariance (ANCOVA) with terms for treatment, baseline value, prior therapy, and region.

Outcome measures

Outcome measures
Measure	Rosiglitazone in DB Period; Metformin in OL Period n=65 Participants Rosiglitazone (RSG) initiated at a total daily dose of 4 milligrams (mg) in the 52-week DB Period. RSG could be uptitrated to a total daily dose of 8 mg at Week 4. At Week 52, all participants were switched to open-label (OL) Metformin (MET) therapy for 24 weeks during the follow-up phase; all participants were force-titrated from 1000 mg/day to 2000 mg/day over a 4-week period. However, participants could be down-titrated to alleviate any MET-related tolerability issues.	Metformin in DB Period; Metformin in OL Period n=70 Participants Metformin (MET) initiated at a total daily dose of 1000 mg in the 52-week DB Period. MET could be uptitrated to 1500 mg/day at Week 2 and to 2000 mg/day at Week 4. At Week 52, all participants were switched to open-label MET therapy for 24 weeks during the follow-up phase; all participants were force-titrated from 1000 mg/day to 2000 mg/day over a 4-week period. However, participants could be down-titrated to alleviate any MET-related tolerability issues.
Adjusted Percent Change From Baseline in Femoral Neck (FN) Bone Mineral Density (BMD) Via Dual-energy X-ray Absorptiometry (DXA) at Week 76+10 Days	-1.91 percent change Standard Error 0.624	0.31 percent change Standard Error 0.636

PRIMARY outcome

Timeframe: Week 52+10 days and Week 76+10 days

Population: Safety Population. Only evaluable participants with a value at Week 52 performed up to 10 days after initiating OL MET and at Week 76 performed up to 10 days after stopping OL MET for the parameter of interest were analyzed.

FN BMD (measured in grams per centimeters squared \[g/cm\^2\]) was measured by DXA. Bone mineral density is calculated as the mineral content of a bone divided by the area of the bone. DXA is the principal technique used for measuring BMD. Percent change from Week 52+10 days to Week 76+10 days was calculated as (BMD at Week 76+10 days minus BMD at Week 52+10 days)/BMD at Week 52+10 days x 100% and was assessed by analysis of covariance (ANCOVA) with terms for treatment, baseline value, prior therapy, and region.

Outcome measures

Outcome measures
Measure	Rosiglitazone in DB Period; Metformin in OL Period n=56 Participants Rosiglitazone (RSG) initiated at a total daily dose of 4 milligrams (mg) in the 52-week DB Period. RSG could be uptitrated to a total daily dose of 8 mg at Week 4. At Week 52, all participants were switched to open-label (OL) Metformin (MET) therapy for 24 weeks during the follow-up phase; all participants were force-titrated from 1000 mg/day to 2000 mg/day over a 4-week period. However, participants could be down-titrated to alleviate any MET-related tolerability issues.	Metformin in DB Period; Metformin in OL Period n=62 Participants Metformin (MET) initiated at a total daily dose of 1000 mg in the 52-week DB Period. MET could be uptitrated to 1500 mg/day at Week 2 and to 2000 mg/day at Week 4. At Week 52, all participants were switched to open-label MET therapy for 24 weeks during the follow-up phase; all participants were force-titrated from 1000 mg/day to 2000 mg/day over a 4-week period. However, participants could be down-titrated to alleviate any MET-related tolerability issues.
Adjusted Percent Change in Femoral Neck (FN) Bone Mineral Density (BMD) Via Dual-energy X-ray Absorptiometry (DXA) From Week 52 +10 Days to Week 76+10 Days	-0.07 percent change Standard Error 0.589	-0.02 percent change Standard Error 0.585

SECONDARY outcome

Timeframe: Baseline and Week 52

Population: Safety Population. Only evaluable participants with a value at baseline and at Week 52 for the parameter of interest were analyzed. Only participants with Baseline DXA and Week 52 DXA measurements performed on or prior to initiating open-label MET were analyzed. Not all participants had correct positioning for the DXA lumbar spine measurement.

BMD (measured in grams per centimeters squared \[g/cm\^2\]) was measured by DXA. Percent change from Baseline at Week 52 was calculated as (BMD at Week 52 minus BMD at Baseline)/BMD at Baseline x 100% and was assessed by analysis of covariance (ANCOVA) with terms for treatment, baseline value, prior therapy, and region.

Outcome measures

Outcome measures
Measure	Rosiglitazone in DB Period; Metformin in OL Period n=52 Participants Rosiglitazone (RSG) initiated at a total daily dose of 4 milligrams (mg) in the 52-week DB Period. RSG could be uptitrated to a total daily dose of 8 mg at Week 4. At Week 52, all participants were switched to open-label (OL) Metformin (MET) therapy for 24 weeks during the follow-up phase; all participants were force-titrated from 1000 mg/day to 2000 mg/day over a 4-week period. However, participants could be down-titrated to alleviate any MET-related tolerability issues.	Metformin in DB Period; Metformin in OL Period n=54 Participants Metformin (MET) initiated at a total daily dose of 1000 mg in the 52-week DB Period. MET could be uptitrated to 1500 mg/day at Week 2 and to 2000 mg/day at Week 4. At Week 52, all participants were switched to open-label MET therapy for 24 weeks during the follow-up phase; all participants were force-titrated from 1000 mg/day to 2000 mg/day over a 4-week period. However, participants could be down-titrated to alleviate any MET-related tolerability issues.
Adjusted Percent Change From Baseline in Femoral Neck, Total Hip, Trochanter, and Lumbar Spine BMD Via DXA at Week 52 Femoral neck, n=52, 54	-1.24 percent change Standard Error 0.619	0.72 percent change Standard Error 0.659
Adjusted Percent Change From Baseline in Femoral Neck, Total Hip, Trochanter, and Lumbar Spine BMD Via DXA at Week 52 Total hip, n=52, 54	-0.77 percent change Standard Error 0.417	-0.38 percent change Standard Error 0.440
Adjusted Percent Change From Baseline in Femoral Neck, Total Hip, Trochanter, and Lumbar Spine BMD Via DXA at Week 52 Trochanter, n=52, 54	-0.21 percent change Standard Error 0.725	-0.78 percent change Standard Error 0.768
Adjusted Percent Change From Baseline in Femoral Neck, Total Hip, Trochanter, and Lumbar Spine BMD Via DXA at Week 52 Lumbar spine, n=51, 53	-1.21 percent change Standard Error 0.473	0.12 percent change Standard Error 0.505

SECONDARY outcome

Timeframe: Week 52 + 10 days and Week 76 + 10 days

Population: Safety Population. Only evaluable participants with a value at Week 52 performed up to 10 days after initiating OL MET and at Week 76 performed up to 10 days after stopping OL MET for the parameter of interest were analyzed. Not all participants had correct positioning for the DXA lumbar spine measurement.

BMD (measured in grams per centimeters squared \[g/cm\^2\]) was measured by DXA. Percent change from Week 52 + 10 days toat Week 76 + 10 days was calculated as (BMD at Week 76 + 10 days minus BMD at Week 52 + 10 days)/BMD at Week 52 + 10 days x 100% and was assessed by analysis of covariance (ANCOVA) with terms for treatment, baseline value, prior therapy, and region.

Outcome measures

Outcome measures
Measure	Rosiglitazone in DB Period; Metformin in OL Period n=56 Participants Rosiglitazone (RSG) initiated at a total daily dose of 4 milligrams (mg) in the 52-week DB Period. RSG could be uptitrated to a total daily dose of 8 mg at Week 4. At Week 52, all participants were switched to open-label (OL) Metformin (MET) therapy for 24 weeks during the follow-up phase; all participants were force-titrated from 1000 mg/day to 2000 mg/day over a 4-week period. However, participants could be down-titrated to alleviate any MET-related tolerability issues.	Metformin in DB Period; Metformin in OL Period n=62 Participants Metformin (MET) initiated at a total daily dose of 1000 mg in the 52-week DB Period. MET could be uptitrated to 1500 mg/day at Week 2 and to 2000 mg/day at Week 4. At Week 52, all participants were switched to open-label MET therapy for 24 weeks during the follow-up phase; all participants were force-titrated from 1000 mg/day to 2000 mg/day over a 4-week period. However, participants could be down-titrated to alleviate any MET-related tolerability issues.
Adjusted Percent Change in Femoral Neck, Total Hip, Trochanter, and Lumbar Spine BMD Via DXA From Week 52+10 Days to Week 76 + 10 Days Femoral neck, n=56, 62	-0.07 percent change Standard Error 0.589	-0.02 percent change Standard Error 0.585
Adjusted Percent Change in Femoral Neck, Total Hip, Trochanter, and Lumbar Spine BMD Via DXA From Week 52+10 Days to Week 76 + 10 Days Total hip, n=56, 62	0.40 percent change Standard Error 0.304	-0.13 percent change Standard Error 0.301
Adjusted Percent Change in Femoral Neck, Total Hip, Trochanter, and Lumbar Spine BMD Via DXA From Week 52+10 Days to Week 76 + 10 Days Trochanter, n=56, 62	-0.02 percent change Standard Error 0.475	-0.68 percent change Standard Error 0.469
Adjusted Percent Change in Femoral Neck, Total Hip, Trochanter, and Lumbar Spine BMD Via DXA From Week 52+10 Days to Week 76 + 10 Days Lumbar spine, n=55, 62	0.26 percent change Standard Error 0.440	1.03 percent change Standard Error 0.442

SECONDARY outcome

Timeframe: Week 52 + 30 days and Week 76 + 30 days

Population: Safety Population. Only evaluable participants with a value at Week 52 performed up to 30 days after initiating OL MET and Week 76 performed up to 30 days after stopping OL MET for the parameter of interest were analyzed. Not all participants had correct positioning for all of the DXA measurements.

BMD (measured in grams per centimeters squared \[g/cm\^2\]) was measured by DXA. Percent change from Week 52 + 30 days to Week 76 + 30 days was calculated as (BMD at Week 76 + 30 days minus BMD at Week 52 + 30 days)/BMD at Week 52 + 30 days x 100% and was assessed by analysis of covariance (ANCOVA) with terms for treatment, baseline value, prior therapy, and region.

Outcome measures

Outcome measures
Measure	Rosiglitazone in DB Period; Metformin in OL Period n=65 Participants Rosiglitazone (RSG) initiated at a total daily dose of 4 milligrams (mg) in the 52-week DB Period. RSG could be uptitrated to a total daily dose of 8 mg at Week 4. At Week 52, all participants were switched to open-label (OL) Metformin (MET) therapy for 24 weeks during the follow-up phase; all participants were force-titrated from 1000 mg/day to 2000 mg/day over a 4-week period. However, participants could be down-titrated to alleviate any MET-related tolerability issues.	Metformin in DB Period; Metformin in OL Period n=73 Participants Metformin (MET) initiated at a total daily dose of 1000 mg in the 52-week DB Period. MET could be uptitrated to 1500 mg/day at Week 2 and to 2000 mg/day at Week 4. At Week 52, all participants were switched to open-label MET therapy for 24 weeks during the follow-up phase; all participants were force-titrated from 1000 mg/day to 2000 mg/day over a 4-week period. However, participants could be down-titrated to alleviate any MET-related tolerability issues.
Adjusted Percent Change in Femoral Neck, Total Hip, Trochanter, and Lumbar Spine BMD Via DXA From Week 52+30 Days to Week 76 + 30 Days Femoral neck, n=64, 73	-0.27 percent change Standard Error 0.559	-0.25 percent change Standard Error 0.535
Adjusted Percent Change in Femoral Neck, Total Hip, Trochanter, and Lumbar Spine BMD Via DXA From Week 52+30 Days to Week 76 + 30 Days Total hip, n=64, 73	0.00 percent change Standard Error 0.298	-0.27 percent change Standard Error 0.283
Adjusted Percent Change in Femoral Neck, Total Hip, Trochanter, and Lumbar Spine BMD Via DXA From Week 52+30 Days to Week 76 + 30 Days Trochanter, n=64, 73	-0.17 percent change Standard Error 0.495	-0.47 percent change Standard Error 0.470
Adjusted Percent Change in Femoral Neck, Total Hip, Trochanter, and Lumbar Spine BMD Via DXA From Week 52+30 Days to Week 76 + 30 Days Lumbar spine, n=65, 70	0.54 percent change Standard Error 0.445	0.90 percent change Standard Error 0.442

SECONDARY outcome

Timeframe: Baseline, Week 52, and Week 76

Population: Safety Population. Only evaluable participants with a value at Baseline and at Week 52 or Week 76 for the parameter of interest were analyzed.

BSAP and P1NP levels were measured in micrograms per liter (mcg/L) from blood samples. BSAP and P1NP are indicators of bone buildup or formation. GM, geometric mean; SE, standard error. Percent change was based on log-transformed data and was assessed by an ANCOVA with terms for treatment, baseline value, prior therapy, and region.

Outcome measures

Outcome measures
Measure	Rosiglitazone in DB Period; Metformin in OL Period n=78 Participants Rosiglitazone (RSG) initiated at a total daily dose of 4 milligrams (mg) in the 52-week DB Period. RSG could be uptitrated to a total daily dose of 8 mg at Week 4. At Week 52, all participants were switched to open-label (OL) Metformin (MET) therapy for 24 weeks during the follow-up phase; all participants were force-titrated from 1000 mg/day to 2000 mg/day over a 4-week period. However, participants could be down-titrated to alleviate any MET-related tolerability issues.	Metformin in DB Period; Metformin in OL Period n=84 Participants Metformin (MET) initiated at a total daily dose of 1000 mg in the 52-week DB Period. MET could be uptitrated to 1500 mg/day at Week 2 and to 2000 mg/day at Week 4. At Week 52, all participants were switched to open-label MET therapy for 24 weeks during the follow-up phase; all participants were force-titrated from 1000 mg/day to 2000 mg/day over a 4-week period. However, participants could be down-titrated to alleviate any MET-related tolerability issues.
Adjusted Percent Change From Baseline in Bone Specific Alkaline Phosphatase (BSAP) and Procollagen Type 1 N-propeptide (P1NP) at Week 52 and Week 76 Week 52, GM - SE, BSAP, n=78, 84	-15.2 percent change	-29.7 percent change
Adjusted Percent Change From Baseline in Bone Specific Alkaline Phosphatase (BSAP) and Procollagen Type 1 N-propeptide (P1NP) at Week 52 and Week 76 Week 52, GM, BSAP, n=78, 84	-12.3 percent change	-27.3 percent change
Adjusted Percent Change From Baseline in Bone Specific Alkaline Phosphatase (BSAP) and Procollagen Type 1 N-propeptide (P1NP) at Week 52 and Week 76 Week 52, GM + SE, BSAP, n=78, 84	-9.3 percent change	-24.8 percent change
Adjusted Percent Change From Baseline in Bone Specific Alkaline Phosphatase (BSAP) and Procollagen Type 1 N-propeptide (P1NP) at Week 52 and Week 76 Week 76, GM - SE, BSAP, n=64, 77	-18.7 percent change	-26.7 percent change
Adjusted Percent Change From Baseline in Bone Specific Alkaline Phosphatase (BSAP) and Procollagen Type 1 N-propeptide (P1NP) at Week 52 and Week 76 Week 76, GM, BSAP, n=64, 77	-15.9 percent change	-24.3 percent change
Adjusted Percent Change From Baseline in Bone Specific Alkaline Phosphatase (BSAP) and Procollagen Type 1 N-propeptide (P1NP) at Week 52 and Week 76 Week 76, GM + SE, BSAP, n=64, 77	-12.9 percent change	-21.8 percent change
Adjusted Percent Change From Baseline in Bone Specific Alkaline Phosphatase (BSAP) and Procollagen Type 1 N-propeptide (P1NP) at Week 52 and Week 76 Week 52, GM - SE, P1NP, n=76, 83	5.0 percent change	-16.5 percent change
Adjusted Percent Change From Baseline in Bone Specific Alkaline Phosphatase (BSAP) and Procollagen Type 1 N-propeptide (P1NP) at Week 52 and Week 76 Week 52, GM, P1NP, n=76, 83	9.0 percent change	-13.3 percent change
Adjusted Percent Change From Baseline in Bone Specific Alkaline Phosphatase (BSAP) and Procollagen Type 1 N-propeptide (P1NP) at Week 52 and Week 76 Week 52, GM + SE, P1NP, n=76, 83	13.3 percent change	-9.9 percent change
Adjusted Percent Change From Baseline in Bone Specific Alkaline Phosphatase (BSAP) and Procollagen Type 1 N-propeptide (P1NP) at Week 52 and Week 76 Week 76 GM - SE, P1NP, n=63, 75	-11.2 percent change	-14.5 percent change
Adjusted Percent Change From Baseline in Bone Specific Alkaline Phosphatase (BSAP) and Procollagen Type 1 N-propeptide (P1NP) at Week 52 and Week 76 Week 76, GM, P1NP, n=63, 75	-6.9 percent change	-10.5 percent change
Adjusted Percent Change From Baseline in Bone Specific Alkaline Phosphatase (BSAP) and Procollagen Type 1 N-propeptide (P1NP) at Week 52 and Week 76 Week 76, GM + SE, P1NP, n=63, 75	-2.4 percent change	-6.4 percent change

SECONDARY outcome

Timeframe: Week 52 and Week 76

Population: Safety Population. Only evaluable participants with a value at Week 52 and at Week 76 for the parameter of interest were analyzed. One participant did not have P1NP measured.

BSAP and P1NP levels were measured in micrograms per liter (mcg/L) from blood samples. BSAP and P1NP are indicators of bone buildup or formation. GM, geometric mean; SE, standard error. Percent change was based on log-transformed data and was assessed by an ANCOVA with terms for treatment, baseline value, prior therapy, and region.

Outcome measures

Outcome measures
Measure	Rosiglitazone in DB Period; Metformin in OL Period n=64 Participants Rosiglitazone (RSG) initiated at a total daily dose of 4 milligrams (mg) in the 52-week DB Period. RSG could be uptitrated to a total daily dose of 8 mg at Week 4. At Week 52, all participants were switched to open-label (OL) Metformin (MET) therapy for 24 weeks during the follow-up phase; all participants were force-titrated from 1000 mg/day to 2000 mg/day over a 4-week period. However, participants could be down-titrated to alleviate any MET-related tolerability issues.	Metformin in DB Period; Metformin in OL Period n=76 Participants Metformin (MET) initiated at a total daily dose of 1000 mg in the 52-week DB Period. MET could be uptitrated to 1500 mg/day at Week 2 and to 2000 mg/day at Week 4. At Week 52, all participants were switched to open-label MET therapy for 24 weeks during the follow-up phase; all participants were force-titrated from 1000 mg/day to 2000 mg/day over a 4-week period. However, participants could be down-titrated to alleviate any MET-related tolerability issues.
Adjusted Percent Change in Bone Specific Alkaline Phosphatase (BSAP) and Procollagen Type 1 N-propeptide (P1NP) From Week 52 to Week 76 GM - SE, BSAP, n=64, 76	-5.6 percent change	4.3 percent change
Adjusted Percent Change in Bone Specific Alkaline Phosphatase (BSAP) and Procollagen Type 1 N-propeptide (P1NP) From Week 52 to Week 76 GM, BSAP, n=64, 76	-2.0 percent change	8.0 percent change
Adjusted Percent Change in Bone Specific Alkaline Phosphatase (BSAP) and Procollagen Type 1 N-propeptide (P1NP) From Week 52 to Week 76 GM + SE, BSAP, n=64, 76	1.8 percent change	11.8 percent change
Adjusted Percent Change in Bone Specific Alkaline Phosphatase (BSAP) and Procollagen Type 1 N-propeptide (P1NP) From Week 52 to Week 76 GM - SE, P1NP, n=63, 76	-15.8 percent change	3.2 percent change
Adjusted Percent Change in Bone Specific Alkaline Phosphatase (BSAP) and Procollagen Type 1 N-propeptide (P1NP) From Week 52 to Week 76 GM, P1NP, n=63, 76	-12.4 percent change	7.0 percent change
Adjusted Percent Change in Bone Specific Alkaline Phosphatase (BSAP) and Procollagen Type 1 N-propeptide (P1NP) From Week 52 to Week 76 GM + SE, P1NP, n=63, 76	-9.0 percent change	11.0 percent change

SECONDARY outcome

Timeframe: Baseline, Week 52, and Week 76

Population: Safety Population. Only evaluable participants with a value at Baseline and at Week 52 or Week 76 for the parameter of interest were analyzed.

CTX levels were measured in picograms per milliliter (pg/ml) from blood samples. CTX is an indicator of bone break down or resorption. Percent change was based on log-transformed data and was assessed by an ANCOVA with terms for treatment, baseline value, prior therapy, and region.

Outcome measures

Outcome measures
Measure	Rosiglitazone in DB Period; Metformin in OL Period n=77 Participants Rosiglitazone (RSG) initiated at a total daily dose of 4 milligrams (mg) in the 52-week DB Period. RSG could be uptitrated to a total daily dose of 8 mg at Week 4. At Week 52, all participants were switched to open-label (OL) Metformin (MET) therapy for 24 weeks during the follow-up phase; all participants were force-titrated from 1000 mg/day to 2000 mg/day over a 4-week period. However, participants could be down-titrated to alleviate any MET-related tolerability issues.	Metformin in DB Period; Metformin in OL Period n=84 Participants Metformin (MET) initiated at a total daily dose of 1000 mg in the 52-week DB Period. MET could be uptitrated to 1500 mg/day at Week 2 and to 2000 mg/day at Week 4. At Week 52, all participants were switched to open-label MET therapy for 24 weeks during the follow-up phase; all participants were force-titrated from 1000 mg/day to 2000 mg/day over a 4-week period. However, participants could be down-titrated to alleviate any MET-related tolerability issues.
Adjusted Percent Change From Baseline in Carboxyterminal Cross-linked Telopeptide of Type 1 Collagen (CTX) at Week 52 and Week 76 Week 52, GM - SE, n=77, 84	11.3 percent change	-7.8 percent change
Adjusted Percent Change From Baseline in Carboxyterminal Cross-linked Telopeptide of Type 1 Collagen (CTX) at Week 52 and Week 76 Week 52, GM, n=77, 84	18.1 percent change	-2.3 percent change
Adjusted Percent Change From Baseline in Carboxyterminal Cross-linked Telopeptide of Type 1 Collagen (CTX) at Week 52 and Week 76 Week 52, GM + SE, n=77, 84	25.4 percent change	3.7 percent change
Adjusted Percent Change From Baseline in Carboxyterminal Cross-linked Telopeptide of Type 1 Collagen (CTX) at Week 52 and Week 76 Week 76, GM - SE, n=63, 77	-19.5 percent change	-4.5 percent change
Adjusted Percent Change From Baseline in Carboxyterminal Cross-linked Telopeptide of Type 1 Collagen (CTX) at Week 52 and Week 76 Week 76, GM, n=63, 77	-13.1 percent change	2.6 percent change
Adjusted Percent Change From Baseline in Carboxyterminal Cross-linked Telopeptide of Type 1 Collagen (CTX) at Week 52 and Week 76 Week 76, GM + SE, n=63, 77	-6.1 percent change	10.3 percent change

SECONDARY outcome

Timeframe: Week 52 and Week 76

Population: Safety Population. Only evaluable participants with a value at Week 52 and at Week 76 for the parameter of interest were analyzed.

CTX levels were measured in picograms per milliliter (pg/ml) from blood samples. CTX is an indicator of bone break down or resorption. Percent change was based on log-transformed data and was assessed by an ANCOVA with terms for treatment, baseline value, prior therapy, and region.

Outcome measures

Outcome measures
Measure	Rosiglitazone in DB Period; Metformin in OL Period n=64 Participants Rosiglitazone (RSG) initiated at a total daily dose of 4 milligrams (mg) in the 52-week DB Period. RSG could be uptitrated to a total daily dose of 8 mg at Week 4. At Week 52, all participants were switched to open-label (OL) Metformin (MET) therapy for 24 weeks during the follow-up phase; all participants were force-titrated from 1000 mg/day to 2000 mg/day over a 4-week period. However, participants could be down-titrated to alleviate any MET-related tolerability issues.	Metformin in DB Period; Metformin in OL Period n=76 Participants Metformin (MET) initiated at a total daily dose of 1000 mg in the 52-week DB Period. MET could be uptitrated to 1500 mg/day at Week 2 and to 2000 mg/day at Week 4. At Week 52, all participants were switched to open-label MET therapy for 24 weeks during the follow-up phase; all participants were force-titrated from 1000 mg/day to 2000 mg/day over a 4-week period. However, participants could be down-titrated to alleviate any MET-related tolerability issues.
Adjusted Percent Change in Carboxyterminal Cross-linked Telopeptide of Type 1 Collagen (CTX) From Week 52 to Week 76 GM - SE	-31.2 percent change	2.2 percent change
Adjusted Percent Change in Carboxyterminal Cross-linked Telopeptide of Type 1 Collagen (CTX) From Week 52 to Week 76 GM	-26.7 percent change	8.4 percent change
Adjusted Percent Change in Carboxyterminal Cross-linked Telopeptide of Type 1 Collagen (CTX) From Week 52 to Week 76 GM + SE	-21.9 percent change	14.9 percent change

SECONDARY outcome

Timeframe: Baseline, Week 52, and Week 76

Population: Safety Population. Only evaluable participants with a value at Baseline and at Week 52 or Week 76 for the parameter of interest were analyzed.

Vitamin D levels were measured in nanomoles per Liter (nmol/L) from blood samples. Vitamin D is required for good bone health. Percent change was based on log-transformed data and was assessed by an ANCOVA with terms for treatment, baseline value, prior therapy, and region.

Outcome measures

Outcome measures
Measure	Rosiglitazone in DB Period; Metformin in OL Period n=61 Participants Rosiglitazone (RSG) initiated at a total daily dose of 4 milligrams (mg) in the 52-week DB Period. RSG could be uptitrated to a total daily dose of 8 mg at Week 4. At Week 52, all participants were switched to open-label (OL) Metformin (MET) therapy for 24 weeks during the follow-up phase; all participants were force-titrated from 1000 mg/day to 2000 mg/day over a 4-week period. However, participants could be down-titrated to alleviate any MET-related tolerability issues.	Metformin in DB Period; Metformin in OL Period n=65 Participants Metformin (MET) initiated at a total daily dose of 1000 mg in the 52-week DB Period. MET could be uptitrated to 1500 mg/day at Week 2 and to 2000 mg/day at Week 4. At Week 52, all participants were switched to open-label MET therapy for 24 weeks during the follow-up phase; all participants were force-titrated from 1000 mg/day to 2000 mg/day over a 4-week period. However, participants could be down-titrated to alleviate any MET-related tolerability issues.
Adjusted Percent Change From Baseline in 25-Hydroxyvitamin D (Vitamin D) at Week 52 and Week 76 Week 52, GM - SE, n=61, 65	-27.9 percent change	-15.9 percent change
Adjusted Percent Change From Baseline in 25-Hydroxyvitamin D (Vitamin D) at Week 52 and Week 76 Week 52, GM, n=61, 65	-24.7 percent change	-12.2 percent change
Adjusted Percent Change From Baseline in 25-Hydroxyvitamin D (Vitamin D) at Week 52 and Week 76 Week 52, GM + SE, n=61, 65	-21.4 percent change	-8.4 percent change
Adjusted Percent Change From Baseline in 25-Hydroxyvitamin D (Vitamin D) at Week 52 and Week 76 Week 76, GM - SE, n=55, 58	-21.3 percent change	-12.5 percent change
Adjusted Percent Change From Baseline in 25-Hydroxyvitamin D (Vitamin D) at Week 52 and Week 76 Week 76, GM, n=55, 58	-18.1 percent change	-8.9 percent change
Adjusted Percent Change From Baseline in 25-Hydroxyvitamin D (Vitamin D) at Week 52 and Week 76 Week 76, GM + SE, n=55, 58	-14.6 percent change	-5.2 percent change

SECONDARY outcome

Timeframe: Week 52 and Week 76

Population: Safety Population. Only evaluable participants with a value at Week 52 and at Week 76 for the parameter of interest were analyzed.

Vitamin D levels were measured in nanomoles per Liter (nmol/L) from blood samples. Vitamin D is required for good bone health. Percent change was based on log-transformed data and was assessed by an ANCOVA with terms for treatment, baseline value, prior therapy, and region.

Outcome measures

Outcome measures
Measure	Rosiglitazone in DB Period; Metformin in OL Period n=63 Participants Rosiglitazone (RSG) initiated at a total daily dose of 4 milligrams (mg) in the 52-week DB Period. RSG could be uptitrated to a total daily dose of 8 mg at Week 4. At Week 52, all participants were switched to open-label (OL) Metformin (MET) therapy for 24 weeks during the follow-up phase; all participants were force-titrated from 1000 mg/day to 2000 mg/day over a 4-week period. However, participants could be down-titrated to alleviate any MET-related tolerability issues.	Metformin in DB Period; Metformin in OL Period n=76 Participants Metformin (MET) initiated at a total daily dose of 1000 mg in the 52-week DB Period. MET could be uptitrated to 1500 mg/day at Week 2 and to 2000 mg/day at Week 4. At Week 52, all participants were switched to open-label MET therapy for 24 weeks during the follow-up phase; all participants were force-titrated from 1000 mg/day to 2000 mg/day over a 4-week period. However, participants could be down-titrated to alleviate any MET-related tolerability issues.
Adjusted Percent Change in 25-Hydroxyvitamin D (Vitamin D) From Week 52 to Week 76 GM - SE	-4.7 percent change	-7.7 percent change
Adjusted Percent Change in 25-Hydroxyvitamin D (Vitamin D) From Week 52 to Week 76 GM	0.1 percent change	-3.2 percent change
Adjusted Percent Change in 25-Hydroxyvitamin D (Vitamin D) From Week 52 to Week 76 GM + SE	5.1 percent change	1.5 percent change

SECONDARY outcome

Timeframe: Baseline, Week 52, and Week 76

Population: Safety Population. Only evaluable participants with a value at Baseline and at Week 52 or Week 76 for the parameter of interest were analyzed.

Intact PTH levels were measured in nanograms per Liter (ng/L) from blood samples. Intact PTH is the amount of PTH circulating in the blood and influences bone health. Percent change was based on log-transformed data and was assessed by an ANCOVA with terms for treatment, baseline value, prior therapy, and region.

Outcome measures

Outcome measures
Measure	Rosiglitazone in DB Period; Metformin in OL Period n=64 Participants Rosiglitazone (RSG) initiated at a total daily dose of 4 milligrams (mg) in the 52-week DB Period. RSG could be uptitrated to a total daily dose of 8 mg at Week 4. At Week 52, all participants were switched to open-label (OL) Metformin (MET) therapy for 24 weeks during the follow-up phase; all participants were force-titrated from 1000 mg/day to 2000 mg/day over a 4-week period. However, participants could be down-titrated to alleviate any MET-related tolerability issues.	Metformin in DB Period; Metformin in OL Period n=71 Participants Metformin (MET) initiated at a total daily dose of 1000 mg in the 52-week DB Period. MET could be uptitrated to 1500 mg/day at Week 2 and to 2000 mg/day at Week 4. At Week 52, all participants were switched to open-label MET therapy for 24 weeks during the follow-up phase; all participants were force-titrated from 1000 mg/day to 2000 mg/day over a 4-week period. However, participants could be down-titrated to alleviate any MET-related tolerability issues.
Adjusted Percent Change From Baseline in Intact Parathyroid Hormone (PTH) at Week 52 and Week 76 Week 52, GM - SE, n=64, 71	-16.5 percent change	-25.9 percent change
Adjusted Percent Change From Baseline in Intact Parathyroid Hormone (PTH) at Week 52 and Week 76 Week 52, GM, n=64, 71	-12.0 percent change	-22.0 percent change
Adjusted Percent Change From Baseline in Intact Parathyroid Hormone (PTH) at Week 52 and Week 76 Week 52, GM + SE, n=64, 71	-7.2 percent change	-17.8 percent change
Adjusted Percent Change From Baseline in Intact Parathyroid Hormone (PTH) at Week 52 and Week 76 Week 76, GM - SE, n=56, 64	-28.8 percent change	-26.2 percent change
Adjusted Percent Change From Baseline in Intact Parathyroid Hormone (PTH) at Week 52 and Week 76 Week 76, GM, n=56, 64	-23.1 percent change	-20.8 percent change
Adjusted Percent Change From Baseline in Intact Parathyroid Hormone (PTH) at Week 52 and Week 76 Week 76, GM + SE, n=56, 64	-17.0 percent change	-15.0 percent change

SECONDARY outcome

Timeframe: Week 52 and Week 76

Population: Safety Population. Only evaluable participants with a value at Week 52 and at Week 76 for the parameter of interest were analyzed.

Intact PTH levels were measured in nanograms per Liter (ng/L) from blood samples. Intact PTH is the amount of PTH circulating in the blood and influences bone health. Percent change was based on log-transformed data and was assessed by an ANCOVA with terms for treatment, baseline value, prior therapy, and region.

Outcome measures

Outcome measures
Measure	Rosiglitazone in DB Period; Metformin in OL Period n=64 Participants Rosiglitazone (RSG) initiated at a total daily dose of 4 milligrams (mg) in the 52-week DB Period. RSG could be uptitrated to a total daily dose of 8 mg at Week 4. At Week 52, all participants were switched to open-label (OL) Metformin (MET) therapy for 24 weeks during the follow-up phase; all participants were force-titrated from 1000 mg/day to 2000 mg/day over a 4-week period. However, participants could be down-titrated to alleviate any MET-related tolerability issues.	Metformin in DB Period; Metformin in OL Period n=75 Participants Metformin (MET) initiated at a total daily dose of 1000 mg in the 52-week DB Period. MET could be uptitrated to 1500 mg/day at Week 2 and to 2000 mg/day at Week 4. At Week 52, all participants were switched to open-label MET therapy for 24 weeks during the follow-up phase; all participants were force-titrated from 1000 mg/day to 2000 mg/day over a 4-week period. However, participants could be down-titrated to alleviate any MET-related tolerability issues.
Adjusted Percent Change in Intact Parathyroid Hormone (PTH) From Week 52 to Week 76 GM - SE	-13.2 percent change	-1.7 percent change
Adjusted Percent Change in Intact Parathyroid Hormone (PTH) From Week 52 to Week 76 GM	-7.4 percent change	4.3 percent change
Adjusted Percent Change in Intact Parathyroid Hormone (PTH) From Week 52 to Week 76 GM + SE	-1.3 percent change	10.7 percent change

SECONDARY outcome

Timeframe: Baseline, Week 52, and Week 76

Population: Safety Population. Only evaluable participants with a value at Baseline and at Week 52 or Week 76 for the parameter of interest were analyzed.

Serum estradiol levels were measured in picomoles per Liter (pmol/L) from blood samples. Estradiol is one form of the female sex hormone estrogen and influences bone health. Percent change from baseline was based on log-transformed data.

Outcome measures

Outcome measures
Measure	Rosiglitazone in DB Period; Metformin in OL Period n=74 Participants Rosiglitazone (RSG) initiated at a total daily dose of 4 milligrams (mg) in the 52-week DB Period. RSG could be uptitrated to a total daily dose of 8 mg at Week 4. At Week 52, all participants were switched to open-label (OL) Metformin (MET) therapy for 24 weeks during the follow-up phase; all participants were force-titrated from 1000 mg/day to 2000 mg/day over a 4-week period. However, participants could be down-titrated to alleviate any MET-related tolerability issues.	Metformin in DB Period; Metformin in OL Period n=82 Participants Metformin (MET) initiated at a total daily dose of 1000 mg in the 52-week DB Period. MET could be uptitrated to 1500 mg/day at Week 2 and to 2000 mg/day at Week 4. At Week 52, all participants were switched to open-label MET therapy for 24 weeks during the follow-up phase; all participants were force-titrated from 1000 mg/day to 2000 mg/day over a 4-week period. However, participants could be down-titrated to alleviate any MET-related tolerability issues.
Percent Change From Baseline in Serum Estradiol at Week 52 and Week 76 Week 52, GM - SE, n=74, 82	-17.0838 percent change	-31.4166 percent change
Percent Change From Baseline in Serum Estradiol at Week 52 and Week 76 Week 52, GM, n=74, 82	-3.453 percent change	-17.280 percent change
Percent Change From Baseline in Serum Estradiol at Week 52 and Week 76 Weel 52, GM + SE, n=74, 82	12.4189 percent change	-0.2292 percent change
Percent Change From Baseline in Serum Estradiol at Week 52 and Week 76 Week 76, GM - SE, n=64, 76	-16.0971 percent change	0.4372 percent change
Percent Change From Baseline in Serum Estradiol at Week 52 and Week 76 Week 76, GM, n=64, 76	0.215 percent change	21.389 percent change
Percent Change From Baseline in Serum Estradiol at Week 52 and Week 76 Week 76, GM + SE, n=64, 76	19.6987 percent change	46.7122 percent change

SECONDARY outcome

Timeframe: Week 52 and Week 76

Population: Safety Population. Only evaluable participants with a value at Week 52 and at Week 76 for the parameter of interest were analyzed.

Serum estradiol levels were measured in picomoles per Liter (pmol/L) from blood samples. Estradiol is one form of the female sex hormone estrogen and influences bone health. Percent change from baseline was based on log-transformed data.

Outcome measures

Outcome measures
Measure	Rosiglitazone in DB Period; Metformin in OL Period n=64 Participants Rosiglitazone (RSG) initiated at a total daily dose of 4 milligrams (mg) in the 52-week DB Period. RSG could be uptitrated to a total daily dose of 8 mg at Week 4. At Week 52, all participants were switched to open-label (OL) Metformin (MET) therapy for 24 weeks during the follow-up phase; all participants were force-titrated from 1000 mg/day to 2000 mg/day over a 4-week period. However, participants could be down-titrated to alleviate any MET-related tolerability issues.	Metformin in DB Period; Metformin in OL Period n=77 Participants Metformin (MET) initiated at a total daily dose of 1000 mg in the 52-week DB Period. MET could be uptitrated to 1500 mg/day at Week 2 and to 2000 mg/day at Week 4. At Week 52, all participants were switched to open-label MET therapy for 24 weeks during the follow-up phase; all participants were force-titrated from 1000 mg/day to 2000 mg/day over a 4-week period. However, participants could be down-titrated to alleviate any MET-related tolerability issues.
Percent Change in Serum Estradiol From Week 52 to Week 76 GM - SE	-15.2056 percent change	29.3058 percent change
Percent Change in Serum Estradiol From Week 52 to Week 76 GM	0.513 percent change	50.823 percent change
Percent Change in Serum Estradiol From Week 52 to Week 76 GM + SE	19.1447 percent change	75.9217 percent change

SECONDARY outcome

Timeframe: Baseline, Week 52, and Week 76

Population: Safety Population. Only evaluable participants with a value at Baseline and at Week 52 or Week 76 for the parameter of interest were analyzed.

Total testosterone levels were measured in nanomoles per Liter (nmol/L) from blood samples. Testosterone is a male sex hormone and influences bone health; total testosterone is the entire amount circulating in blood. Percent change from baseline was based on log-transformed data.

Outcome measures

Outcome measures
Measure	Rosiglitazone in DB Period; Metformin in OL Period n=74 Participants Rosiglitazone (RSG) initiated at a total daily dose of 4 milligrams (mg) in the 52-week DB Period. RSG could be uptitrated to a total daily dose of 8 mg at Week 4. At Week 52, all participants were switched to open-label (OL) Metformin (MET) therapy for 24 weeks during the follow-up phase; all participants were force-titrated from 1000 mg/day to 2000 mg/day over a 4-week period. However, participants could be down-titrated to alleviate any MET-related tolerability issues.	Metformin in DB Period; Metformin in OL Period n=82 Participants Metformin (MET) initiated at a total daily dose of 1000 mg in the 52-week DB Period. MET could be uptitrated to 1500 mg/day at Week 2 and to 2000 mg/day at Week 4. At Week 52, all participants were switched to open-label MET therapy for 24 weeks during the follow-up phase; all participants were force-titrated from 1000 mg/day to 2000 mg/day over a 4-week period. However, participants could be down-titrated to alleviate any MET-related tolerability issues.
Percent Change From Baseline in Total Testosterone at Week 52 and Week 76 Week 52, GM - SE, n=74, 82	14.1569 percent change	-5.8206 percent change
Percent Change From Baseline in Total Testosterone at Week 52 and Week 76 Week 52, GM, n=74, 82	19.689 percent change	1.044 percent change
Percent Change From Baseline in Total Testosterone at Week 52 and Week 76 Week 52, GM + SE, n=74, 82	25.4897 percent change	8.4082 percent change
Percent Change From Baseline in Total Testosterone at Week 52 and Week 76 Week 76, GM - SE, n=64, 75	-12.5441 percent change	-8.2870 percent change
Percent Change From Baseline in Total Testosterone at Week 52 and Week 76 Week 76, GM, n=64, 75	-8.156 percent change	-2.932 percent change
Percent Change From Baseline in Total Testosterone at Week 52 and Week 76 Week 76, GM + SE, n=64, 75	-3.5470 percent change	2.7363 percent change

SECONDARY outcome

Timeframe: Week 52 and Week 76

Population: Safety Population. Only evaluable participants with a value at Week 52 and at Week 76 for the parameter of interest were analyzed.

Total testosterone levels were measured in nanomoles per Liter (nmol/L) from blood samples. Testosterone is a male sex hormone and influences bone health; total testosterone is the entire amount circulating in blood. Percent change from baseline was based on log-transformed data.

Outcome measures

Outcome measures
Measure	Rosiglitazone in DB Period; Metformin in OL Period n=64 Participants Rosiglitazone (RSG) initiated at a total daily dose of 4 milligrams (mg) in the 52-week DB Period. RSG could be uptitrated to a total daily dose of 8 mg at Week 4. At Week 52, all participants were switched to open-label (OL) Metformin (MET) therapy for 24 weeks during the follow-up phase; all participants were force-titrated from 1000 mg/day to 2000 mg/day over a 4-week period. However, participants could be down-titrated to alleviate any MET-related tolerability issues.	Metformin in DB Period; Metformin in OL Period n=76 Participants Metformin (MET) initiated at a total daily dose of 1000 mg in the 52-week DB Period. MET could be uptitrated to 1500 mg/day at Week 2 and to 2000 mg/day at Week 4. At Week 52, all participants were switched to open-label MET therapy for 24 weeks during the follow-up phase; all participants were force-titrated from 1000 mg/day to 2000 mg/day over a 4-week period. However, participants could be down-titrated to alleviate any MET-related tolerability issues.
Percent Change in Total Testosterone From Week 52 to Week 76 GM - SE	-29.0307 percent change	-13.9923 percent change
Percent Change in Total Testosterone From Week 52 to Week 76 GM	-24.373 percent change	-7.102 percent change
Percent Change in Total Testosterone From Week 52 to Week 76 GM + SE	-19.4104 percent change	0.3411 percent change

SECONDARY outcome

Timeframe: Baseline, Week 52, and Week 76

Population: Safety Population. Only evaluable participants with a value at Baseline and at Week 52 or Week 76 for the parameter of interest were analyzed.

Free testosterone levels were measured as a percentage of total testosterone from blood samples. Free testosterone is the amount of testosterone available to the body for use. Percent change from baseline was based on log-transformed data.

Outcome measures

Outcome measures
Measure	Rosiglitazone in DB Period; Metformin in OL Period n=74 Participants Rosiglitazone (RSG) initiated at a total daily dose of 4 milligrams (mg) in the 52-week DB Period. RSG could be uptitrated to a total daily dose of 8 mg at Week 4. At Week 52, all participants were switched to open-label (OL) Metformin (MET) therapy for 24 weeks during the follow-up phase; all participants were force-titrated from 1000 mg/day to 2000 mg/day over a 4-week period. However, participants could be down-titrated to alleviate any MET-related tolerability issues.	Metformin in DB Period; Metformin in OL Period n=82 Participants Metformin (MET) initiated at a total daily dose of 1000 mg in the 52-week DB Period. MET could be uptitrated to 1500 mg/day at Week 2 and to 2000 mg/day at Week 4. At Week 52, all participants were switched to open-label MET therapy for 24 weeks during the follow-up phase; all participants were force-titrated from 1000 mg/day to 2000 mg/day over a 4-week period. However, participants could be down-titrated to alleviate any MET-related tolerability issues.
Percent Change From Baseline in Free Testosterone at Week 52 and Week 76 Week 76, GM, n=64, 75	3.687 percent change	2.478 percent change
Percent Change From Baseline in Free Testosterone at Week 52 and Week 76 Week 76, GM + SE, n=64, 75	7.8593 percent change	7.1093 percent change
Percent Change From Baseline in Free Testosterone at Week 52 and Week 76 Week 52, GM - SE, n=74, 82	-9.9964 percent change	2.5725 percent change
Percent Change From Baseline in Free Testosterone at Week 52 and Week 76 Week 52, GM, n=74, 82	-5.940 percent change	6.266 percent change
Percent Change From Baseline in Free Testosterone at Week 52 and Week 76 Week 52, GM + SE, n=74, 82	1.7006 percent change	10.0934 percent change
Percent Change From Baseline in Free Testosterone at Week 52 and Week 76 Week 76, GM - SE, n=64, 75	-0.3232 percent change	-1.9532 percent change

SECONDARY outcome

Timeframe: Week 52 and Week 76

Population: Safety Population. Only evaluable participants with a value at Week 52 and at Week 76 for the parameter of interest were analyzed.

Free testosterone levels were measured as a percentage of total testosterone from blood samples. Free testosterone is the amount of testosterone available to the body for use. Percent change from baseline was based on log-transformed data.

Outcome measures

Outcome measures
Measure	Rosiglitazone in DB Period; Metformin in OL Period n=64 Participants Rosiglitazone (RSG) initiated at a total daily dose of 4 milligrams (mg) in the 52-week DB Period. RSG could be uptitrated to a total daily dose of 8 mg at Week 4. At Week 52, all participants were switched to open-label (OL) Metformin (MET) therapy for 24 weeks during the follow-up phase; all participants were force-titrated from 1000 mg/day to 2000 mg/day over a 4-week period. However, participants could be down-titrated to alleviate any MET-related tolerability issues.	Metformin in DB Period; Metformin in OL Period n=76 Participants Metformin (MET) initiated at a total daily dose of 1000 mg in the 52-week DB Period. MET could be uptitrated to 1500 mg/day at Week 2 and to 2000 mg/day at Week 4. At Week 52, all participants were switched to open-label MET therapy for 24 weeks during the follow-up phase; all participants were force-titrated from 1000 mg/day to 2000 mg/day over a 4-week period. However, participants could be down-titrated to alleviate any MET-related tolerability issues.
Percent Change in Free Testosterone From Week 52 to Week 76 GM - SE	3.1109 percent change	-6.9549 percent change
Percent Change in Free Testosterone From Week 52 to Week 76 GM	8.993 percent change	-3.537 percent change
Percent Change in Free Testosterone From Week 52 to Week 76 GM + SE	15.2100 percent change	0.0073 percent change

SECONDARY outcome

Timeframe: Baseline, Week 52, and Week 76

Population: Safety Population. Only evaluable participants with a value at Baseline and at Week 52 or Week 76 for the parameter of interest were analyzed.

SHBG levels were measured in nanomoles per liter (nmol/L) from blood samples. SHBG binds to estradiol and testosterone and influences the amount of estradiol or testosterone available to the body for use. Percent change from baseline was based on log-transformed data.

Outcome measures

Outcome measures
Measure	Rosiglitazone in DB Period; Metformin in OL Period n=74 Participants Rosiglitazone (RSG) initiated at a total daily dose of 4 milligrams (mg) in the 52-week DB Period. RSG could be uptitrated to a total daily dose of 8 mg at Week 4. At Week 52, all participants were switched to open-label (OL) Metformin (MET) therapy for 24 weeks during the follow-up phase; all participants were force-titrated from 1000 mg/day to 2000 mg/day over a 4-week period. However, participants could be down-titrated to alleviate any MET-related tolerability issues.	Metformin in DB Period; Metformin in OL Period n=83 Participants Metformin (MET) initiated at a total daily dose of 1000 mg in the 52-week DB Period. MET could be uptitrated to 1500 mg/day at Week 2 and to 2000 mg/day at Week 4. At Week 52, all participants were switched to open-label MET therapy for 24 weeks during the follow-up phase; all participants were force-titrated from 1000 mg/day to 2000 mg/day over a 4-week period. However, participants could be down-titrated to alleviate any MET-related tolerability issues.
Percent Change From Baseline in Sex Hormone Binding Globulin (SHBG) at Week 52 and Week 76 Week 52, GM - SE, n=74, 83	33.2608 percent change	4.3929 percent change
Percent Change From Baseline in Sex Hormone Binding Globulin (SHBG) at Week 52 and Week 76 Week 52, GM, n=74, 83	37.563 percent change	8.146 percent change
Percent Change From Baseline in Sex Hormone Binding Globulin (SHBG) at Week 52 and Week 76 Week 52, GM + SE, n=74, 83	42.0049 percent change	12.0349 percent change
Percent Change From Baseline in Sex Hormone Binding Globulin (SHBG) at Week 52 and Week 76 Week 76, GM - SE, n=61, 67	-0.2973 percent change	4.0983 percent change
Percent Change From Baseline in Sex Hormone Binding Globulin (SHBG) at Week 52 and Week 76 Week 76, GM, n=61, 67	3.137 percent change	9.846 percent change
Percent Change From Baseline in Sex Hormone Binding Globulin (SHBG) at Week 52 and Week 76 Week 76, GM + SE, n=61, 67	6.6896 percent change	15.9116 percent change

SECONDARY outcome

Timeframe: Week 52 and Week 76

Population: Safety Population. Only evaluable participants with a value at Week 52 and at Week 76 for the parameter of interest were analyzed.

SHBG levels were measured in nanomoles per liter (nmol/L) from blood samples. SHBG binds to estradiol and testosterone and influences the amount of estradiol or testosterone available to the body for use. Percent change from baseline was based on log-transformed data.

Outcome measures

Outcome measures
Measure	Rosiglitazone in DB Period; Metformin in OL Period n=62 Participants Rosiglitazone (RSG) initiated at a total daily dose of 4 milligrams (mg) in the 52-week DB Period. RSG could be uptitrated to a total daily dose of 8 mg at Week 4. At Week 52, all participants were switched to open-label (OL) Metformin (MET) therapy for 24 weeks during the follow-up phase; all participants were force-titrated from 1000 mg/day to 2000 mg/day over a 4-week period. However, participants could be down-titrated to alleviate any MET-related tolerability issues.	Metformin in DB Period; Metformin in OL Period n=66 Participants Metformin (MET) initiated at a total daily dose of 1000 mg in the 52-week DB Period. MET could be uptitrated to 1500 mg/day at Week 2 and to 2000 mg/day at Week 4. At Week 52, all participants were switched to open-label MET therapy for 24 weeks during the follow-up phase; all participants were force-titrated from 1000 mg/day to 2000 mg/day over a 4-week period. However, participants could be down-titrated to alleviate any MET-related tolerability issues.
Percent Change in Sex Hormone Binding Globulin (SHBG) From Week 52 to Week 76 GM - SE	-27.0129 percent change	-3.9036 percent change
Percent Change in Sex Hormone Binding Globulin (SHBG) From Week 52 to Week 76 GM	-24.624 percent change	-0.825 percent change
Percent Change in Sex Hormone Binding Globulin (SHBG) From Week 52 to Week 76 GM + SE	-22.1566 percent change	2.3517 percent change

OTHER_PRE_SPECIFIED outcome

Timeframe: Week 52 and Week 76

Population: Safety Population. Only evaluable participants with a value at Week 52 and Week 76 for the parameter of interest were analyzed.

Free estradiol levels were measured as a percentage of serum estrogen from blood samples. Free estradiol is the amount of estrogen available to the body for use. Percent change was based on log-transformed data.

Outcome measures

Outcome measures
Measure	Rosiglitazone in DB Period; Metformin in OL Period n=33 Participants Rosiglitazone (RSG) initiated at a total daily dose of 4 milligrams (mg) in the 52-week DB Period. RSG could be uptitrated to a total daily dose of 8 mg at Week 4. At Week 52, all participants were switched to open-label (OL) Metformin (MET) therapy for 24 weeks during the follow-up phase; all participants were force-titrated from 1000 mg/day to 2000 mg/day over a 4-week period. However, participants could be down-titrated to alleviate any MET-related tolerability issues.	Metformin in DB Period; Metformin in OL Period n=38 Participants Metformin (MET) initiated at a total daily dose of 1000 mg in the 52-week DB Period. MET could be uptitrated to 1500 mg/day at Week 2 and to 2000 mg/day at Week 4. At Week 52, all participants were switched to open-label MET therapy for 24 weeks during the follow-up phase; all participants were force-titrated from 1000 mg/day to 2000 mg/day over a 4-week period. However, participants could be down-titrated to alleviate any MET-related tolerability issues.
Percent Change in Percentage of Free Estradiol From Week 52 to Week 76 GM - SE	-7.6337 percent change	-5.4666 percent change
Percent Change in Percentage of Free Estradiol From Week 52 to Week 76 GM	-2.683 percent change	-0.975 percent change
Percent Change in Percentage of Free Estradiol From Week 52 to Week 76 GM + SE	2.5337 percent change	3.7301 percent change

OTHER_PRE_SPECIFIED outcome

Timeframe: Week 52 and Week 76

Population: Safety Population. Only evaluable participants with a value at Week 52 and Week 76 for the parameter of interest were analyzed.

Free estradiol levels were measured in picomoles per Liter (pmol/L) from blood samples. Free estrodial is the amount of estrogen available to the body for use. Change was based on log-transformed data.

Outcome measures

Outcome measures
Measure	Rosiglitazone in DB Period; Metformin in OL Period n=27 Participants Rosiglitazone (RSG) initiated at a total daily dose of 4 milligrams (mg) in the 52-week DB Period. RSG could be uptitrated to a total daily dose of 8 mg at Week 4. At Week 52, all participants were switched to open-label (OL) Metformin (MET) therapy for 24 weeks during the follow-up phase; all participants were force-titrated from 1000 mg/day to 2000 mg/day over a 4-week period. However, participants could be down-titrated to alleviate any MET-related tolerability issues.	Metformin in DB Period; Metformin in OL Period n=33 Participants Metformin (MET) initiated at a total daily dose of 1000 mg in the 52-week DB Period. MET could be uptitrated to 1500 mg/day at Week 2 and to 2000 mg/day at Week 4. At Week 52, all participants were switched to open-label MET therapy for 24 weeks during the follow-up phase; all participants were force-titrated from 1000 mg/day to 2000 mg/day over a 4-week period. However, participants could be down-titrated to alleviate any MET-related tolerability issues.
Percent Change in Free Estradiol From Week 52 to Week 76 GM - SE	-29.5250 percent change	96.1843 percent change
Percent Change in Free Estradiol From Week 52 to Week 76 GM	-3.239 percent change	173.932 percent change
Percent Change in Free Estradiol From Week 52 to Week 76 GM + SE	32.8525 percent change	282.4903 percent change

POST_HOC outcome

Timeframe: Baseline, Week 52 + 10 days, and Week 76 + 10 days

Population: Safety Population. Only evaluable participants with a value at Baseline and at Week 52 performed up to 10 days after initiating OL MET or at Week 76 performed up to 10 days after stopping OL MET for the parameter of interest were analyzed. Not all participants had the correct positioning for the DXA lumbar spine measurement.

BMD (measured in grams per centimeters squared \[g/cm\^2\]) was measured by DXA. Percent change from Baseline at Week 52 + 10 days or Week 76 + 10 days was calculated as (BMD at Week 52 + 10 days (or Week 76 + 10 days ) minus BMD at Baseline)/BMD at Baseline x 100% and was assessed by analysis of covariance (ANCOVA) with terms for treatment, baseline value, prior therapy, and region.

Outcome measures

Outcome measures
Measure	Rosiglitazone in DB Period; Metformin in OL Period n=70 Participants Rosiglitazone (RSG) initiated at a total daily dose of 4 milligrams (mg) in the 52-week DB Period. RSG could be uptitrated to a total daily dose of 8 mg at Week 4. At Week 52, all participants were switched to open-label (OL) Metformin (MET) therapy for 24 weeks during the follow-up phase; all participants were force-titrated from 1000 mg/day to 2000 mg/day over a 4-week period. However, participants could be down-titrated to alleviate any MET-related tolerability issues.	Metformin in DB Period; Metformin in OL Period n=78 Participants Metformin (MET) initiated at a total daily dose of 1000 mg in the 52-week DB Period. MET could be uptitrated to 1500 mg/day at Week 2 and to 2000 mg/day at Week 4. At Week 52, all participants were switched to open-label MET therapy for 24 weeks during the follow-up phase; all participants were force-titrated from 1000 mg/day to 2000 mg/day over a 4-week period. However, participants could be down-titrated to alleviate any MET-related tolerability issues.
Adjusted Percent Change From Baseline in Femoral Neck, Total Hip, Trochanter, and Lumbar Spine BMD Via DXA at Week 52 + 10 Days and Week 76 + 10 Days Week 52 + 10 days; Femoral neck (FN), n=70, 78	-1.47 percent change Standard Error 0.521	0.22 percent change Standard Error 0.512
Adjusted Percent Change From Baseline in Femoral Neck, Total Hip, Trochanter, and Lumbar Spine BMD Via DXA at Week 52 + 10 Days and Week 76 + 10 Days Week 52 + 10 days; Total hip (TH), n=70, 78	-1.62 percent change Standard Error 0.386	-0.72 percent change Standard Error 0.379
Adjusted Percent Change From Baseline in Femoral Neck, Total Hip, Trochanter, and Lumbar Spine BMD Via DXA at Week 52 + 10 Days and Week 76 + 10 Days Week 52 + 10 days; Trochanter (Tro.), n=70, 78	-1.45 percent change Standard Error 0.602	-1.04 percent change Standard Error 0.589
Adjusted Percent Change From Baseline in Femoral Neck, Total Hip, Trochanter, and Lumbar Spine BMD Via DXA at Week 52 + 10 Days and Week 76 + 10 Days Week 52 + 10 days; Lumbar spine (LS), n=70, 76	-1.41 percent change Standard Error 0.416	0.04 percent change Standard Error 0.419
Adjusted Percent Change From Baseline in Femoral Neck, Total Hip, Trochanter, and Lumbar Spine BMD Via DXA at Week 52 + 10 Days and Week 76 + 10 Days Week 76 + 10 days; FN, n=65, 70	-1.91 percent change Standard Error 0.624	0.31 percent change Standard Error 0.636
Adjusted Percent Change From Baseline in Femoral Neck, Total Hip, Trochanter, and Lumbar Spine BMD Via DXA at Week 52 + 10 Days and Week 76 + 10 Days Week 76 + 10 days; TH, n=65, 70	-1.70 percent change Standard Error 0.415	-0.83 percent change Standard Error 0.420
Adjusted Percent Change From Baseline in Femoral Neck, Total Hip, Trochanter, and Lumbar Spine BMD Via DXA at Week 52 + 10 Days and Week 76 + 10 Days Week 76 + 10 days; Tro., n=65, 70	-2.14 percent change Standard Error 0.644	-1.35 percent change Standard Error 0.650
Adjusted Percent Change From Baseline in Femoral Neck, Total Hip, Trochanter, and Lumbar Spine BMD Via DXA at Week 52 + 10 Days and Week 76 + 10 Days Week 76 + 10 days; LS, n=65, 71	-1.24 percent change Standard Error 0.452	0.85 percent change Standard Error 0.457

POST_HOC outcome

Timeframe: Baseline, Week 52 + 30 days, and Week 76 + 30 days

Population: Safety Population. Only evaluable participants with a value at Baseline and at Week 52 performed up to 30 days after initiating OL MET or at Week 76 performed up to 30 days after stopping OL MET for the parameter of interest were analyzed. Not all participants had the correct positioning for all of the DXA measurements.

BMD (measured in grams per centimeters squared \[g/cm\^2\]) was measured by DXA. Percent change from Baseline at Week 52 + 30 days or Week 76 + 30 days was calculated as (BMD at Week 52 + 30 days (or Week 76 + 30 days) minus BMD at Baseline)/BMD at Baseline x 100% and was assessed by analysis of covariance (ANCOVA) with terms for treatment, baseline value, prior therapy, and region.

Outcome measures

Outcome measures
Measure	Rosiglitazone in DB Period; Metformin in OL Period n=79 Participants Rosiglitazone (RSG) initiated at a total daily dose of 4 milligrams (mg) in the 52-week DB Period. RSG could be uptitrated to a total daily dose of 8 mg at Week 4. At Week 52, all participants were switched to open-label (OL) Metformin (MET) therapy for 24 weeks during the follow-up phase; all participants were force-titrated from 1000 mg/day to 2000 mg/day over a 4-week period. However, participants could be down-titrated to alleviate any MET-related tolerability issues.	Metformin in DB Period; Metformin in OL Period n=83 Participants Metformin (MET) initiated at a total daily dose of 1000 mg in the 52-week DB Period. MET could be uptitrated to 1500 mg/day at Week 2 and to 2000 mg/day at Week 4. At Week 52, all participants were switched to open-label MET therapy for 24 weeks during the follow-up phase; all participants were force-titrated from 1000 mg/day to 2000 mg/day over a 4-week period. However, participants could be down-titrated to alleviate any MET-related tolerability issues.
Adjusted Percent Change From Baseline in Femoral Neck, Total Hip, Trochanter, and Lumbar Spine BMD Via DXA at Week 52 + 30 Days and Week 76 + 30 Days Week 52 + 30 days; Femoral neck (FN), n=77, 83	-1.59 percent change Standard Error 0.503	0.24 percent change Standard Error 0.498
Adjusted Percent Change From Baseline in Femoral Neck, Total Hip, Trochanter, and Lumbar Spine BMD Via DXA at Week 52 + 30 Days and Week 76 + 30 Days Week 52 + 30 days; Total hip (TH), n=77, 83	-1.79 percent change Standard Error 0.370	-0.72 percent change Standard Error 0.364
Adjusted Percent Change From Baseline in Femoral Neck, Total Hip, Trochanter, and Lumbar Spine BMD Via DXA at Week 52 + 30 Days and Week 76 + 30 Days Week 52 + 30 days; Trochanter (Tro.), n=77, 83	-1.83 percent change Standard Error 0.583	-1.01 percent change Standard Error 0.574
Adjusted Percent Change From Baseline in Femoral Neck, Total Hip, Trochanter, and Lumbar Spine BMD Via DXA at Week 52 + 30 Days and Week 76 + 30 Days Week 52 + 30 days; Lumbar spine (LS), n=79, 81	-1.60 percent change Standard Error 0.417	0.11 percent change Standard Error 0.421
Adjusted Percent Change From Baseline in Femoral Neck, Total Hip, Trochanter, and Lumbar Spine BMD Via DXA at Week 52 + 30 Days and Week 76 + 30 Days Week 76 + 30 days; FN, n=66, 74	-2.05 percent change Standard Error 0.620	0.29 percent change Standard Error 0.619
Adjusted Percent Change From Baseline in Femoral Neck, Total Hip, Trochanter, and Lumbar Spine BMD Via DXA at Week 52 + 30 Days and Week 76 + 30 Days Week 76 + 30 days; TH, n=66, 74	-1.79 percent change Standard Error 0.408	-0.68 percent change Standard Error 0.404
Adjusted Percent Change From Baseline in Femoral Neck, Total Hip, Trochanter, and Lumbar Spine BMD Via DXA at Week 52 + 30 Days and Week 76 + 30 Days Week 76 + 30 days; Tro., n=66, 74	-2.53 percent change Standard Error 0.508	-0.96 percent change Standard Error 0.575
Adjusted Percent Change From Baseline in Femoral Neck, Total Hip, Trochanter, and Lumbar Spine BMD Via DXA at Week 52 + 30 Days and Week 76 + 30 Days Week 76 + 30 days; LS, n=66, 72	-1.15 percent change Standard Error 0.464	1.13 percent change Standard Error 0.467

POST_HOC outcome

Timeframe: Baseline, Week 52 + 30 days, and Week 76 + 30 days

Population: Safety Population, QCT subset. Only evaluable participants with a value at Baseline and at Week 52 performed up to 30 days after initiating OL MET or at Week 76 performed up to 30 days after stopping OL MET for the parameter of interest were analyzed.

BMD (measured in grams per centimeters squared \[g/cm\^2\]) was measured by QCT. BMD by QCT is the 2-dimensional volume that mimics the DXA measurement for the same region. Percent change from Baseline at Week 52 + 30 days orWeek 76 + 30 days was calculated as (BMD at Week 52 + 30 days (orWeek 76 + 30 days) minus BMD at baseline)/BMD at Baseline x 100% and was assessed by an analysis of covariance (ANCOVA) with terms for treatment, baseline value, prior therapy, and region.

Outcome measures

Outcome measures
Measure	Rosiglitazone in DB Period; Metformin in OL Period n=32 Participants Rosiglitazone (RSG) initiated at a total daily dose of 4 milligrams (mg) in the 52-week DB Period. RSG could be uptitrated to a total daily dose of 8 mg at Week 4. At Week 52, all participants were switched to open-label (OL) Metformin (MET) therapy for 24 weeks during the follow-up phase; all participants were force-titrated from 1000 mg/day to 2000 mg/day over a 4-week period. However, participants could be down-titrated to alleviate any MET-related tolerability issues.	Metformin in DB Period; Metformin in OL Period n=35 Participants Metformin (MET) initiated at a total daily dose of 1000 mg in the 52-week DB Period. MET could be uptitrated to 1500 mg/day at Week 2 and to 2000 mg/day at Week 4. At Week 52, all participants were switched to open-label MET therapy for 24 weeks during the follow-up phase; all participants were force-titrated from 1000 mg/day to 2000 mg/day over a 4-week period. However, participants could be down-titrated to alleviate any MET-related tolerability issues.
Adjusted Percent Change From Baseline in Femoral Neck, Total Hip, Trochanter, and Intertrochanter Areal BMD Via Quantitative Computed Tomography (QCT) at Week 52 + 30 Days and Week 76 + 30 Days Week 52 + 30 days; Femoral neck (FN), n=32, 35	-2.39 percent change Standard Error 0.895	0.09 percent change Standard Error 0.986
Adjusted Percent Change From Baseline in Femoral Neck, Total Hip, Trochanter, and Intertrochanter Areal BMD Via Quantitative Computed Tomography (QCT) at Week 52 + 30 Days and Week 76 + 30 Days Week 52 + 30 days; Total hip (TH), n=32, 35	-3.39 percent change Standard Error 0.475	0.09 percent change Standard Error 0.521
Adjusted Percent Change From Baseline in Femoral Neck, Total Hip, Trochanter, and Intertrochanter Areal BMD Via Quantitative Computed Tomography (QCT) at Week 52 + 30 Days and Week 76 + 30 Days Week 52 + 30 days; Trochanter (Tro.), n=32, 35	-4.53 percent change Standard Error 0.612	-0.23 percent change Standard Error 0.669
Adjusted Percent Change From Baseline in Femoral Neck, Total Hip, Trochanter, and Intertrochanter Areal BMD Via Quantitative Computed Tomography (QCT) at Week 52 + 30 Days and Week 76 + 30 Days Week 52+30 days; Intertrochanter (Inter.),n=32, 35	-3.36 percent change Standard Error 0.515	0.77 percent change Standard Error 0.565
Adjusted Percent Change From Baseline in Femoral Neck, Total Hip, Trochanter, and Intertrochanter Areal BMD Via Quantitative Computed Tomography (QCT) at Week 52 + 30 Days and Week 76 + 30 Days Week 76+30 days; Femoral neck (FN), n=31, 30	-1.98 percent change Standard Error 0.587	-1.52 percent change Standard Error 0.705
Adjusted Percent Change From Baseline in Femoral Neck, Total Hip, Trochanter, and Intertrochanter Areal BMD Via Quantitative Computed Tomography (QCT) at Week 52 + 30 Days and Week 76 + 30 Days Week 76 + 30 days; TH, n=31, 30	-2.11 percent change Standard Error 0.495	-0.32 percent change Standard Error 0.591
Adjusted Percent Change From Baseline in Femoral Neck, Total Hip, Trochanter, and Intertrochanter Areal BMD Via Quantitative Computed Tomography (QCT) at Week 52 + 30 Days and Week 76 + 30 Days Week 76 + 30 days; Tro., n=31, 30	-2.86 percent change Standard Error 0.752	-1.28 percent change Standard Error 0.892
Adjusted Percent Change From Baseline in Femoral Neck, Total Hip, Trochanter, and Intertrochanter Areal BMD Via Quantitative Computed Tomography (QCT) at Week 52 + 30 Days and Week 76 + 30 Days Week 76 + 30 days; Inter., n=31, 30	-1.66 percent change Standard Error 0.525	0.30 percent change Standard Error 0.627

POST_HOC outcome

Timeframe: Week 52 + 30 days and Week 76 + 30 days

Population: Safety Population, QCT subset. Only evaluable participants with a value at Week 52 performed up to 30 days after initiating OL MET or at Week 76 performed up to 30 days after stopping OL MET for the parameter of interest were analyzed.

BMD (measured in grams per centimeters squared \[g/cm\^2\]) was measured by QCT. BMD by QCT is the 2-dimensional volume that mimics the DXA measurement for the same region. Percent change from Week 52 + 30 days to Week 76 + 30 days was calculated as (BMD at Week 76 + 30 days minus BMD at Week 52 + 30 days)/BMD at Week 52 + 30 days x 100% and was assessed by an analysis of covariance (ANCOVA) with terms for treatment, baseline value, prior therapy, and region.

Outcome measures

Outcome measures
Measure	Rosiglitazone in DB Period; Metformin in OL Period n=30 Participants Rosiglitazone (RSG) initiated at a total daily dose of 4 milligrams (mg) in the 52-week DB Period. RSG could be uptitrated to a total daily dose of 8 mg at Week 4. At Week 52, all participants were switched to open-label (OL) Metformin (MET) therapy for 24 weeks during the follow-up phase; all participants were force-titrated from 1000 mg/day to 2000 mg/day over a 4-week period. However, participants could be down-titrated to alleviate any MET-related tolerability issues.	Metformin in DB Period; Metformin in OL Period n=30 Participants Metformin (MET) initiated at a total daily dose of 1000 mg in the 52-week DB Period. MET could be uptitrated to 1500 mg/day at Week 2 and to 2000 mg/day at Week 4. At Week 52, all participants were switched to open-label MET therapy for 24 weeks during the follow-up phase; all participants were force-titrated from 1000 mg/day to 2000 mg/day over a 4-week period. However, participants could be down-titrated to alleviate any MET-related tolerability issues.
Adjusted Percent Change in Femoral Neck, Total Hip, Trochanter, and Intertrochanter Areal BMD Via Quantitative Computed Tomography (QCT) From Week 52+30 Days to Week 76 + 30 Days percent change	0.95 percent change Standard Error 0.728	-1.39 percent change Standard Error 0.866
Adjusted Percent Change in Femoral Neck, Total Hip, Trochanter, and Intertrochanter Areal BMD Via Quantitative Computed Tomography (QCT) From Week 52+30 Days to Week 76 + 30 Days Total hip	1.61 percent change Standard Error 0.346	-0.18 percent change Standard Error 0.411
Adjusted Percent Change in Femoral Neck, Total Hip, Trochanter, and Intertrochanter Areal BMD Via Quantitative Computed Tomography (QCT) From Week 52+30 Days to Week 76 + 30 Days Trochanter	1.81 percent change Standard Error 0.534	-0.91 percent change Standard Error 0.632
Adjusted Percent Change in Femoral Neck, Total Hip, Trochanter, and Intertrochanter Areal BMD Via Quantitative Computed Tomography (QCT) From Week 52+30 Days to Week 76 + 30 Days Intertrochanter	2.05 percent change Standard Error 0.428	-0.25 percent change Standard Error 0.507

POST_HOC outcome

Timeframe: Baseline, Week 52 + 30 days, and Week 76 + 30 days

Population: Safety Population, QCT subset. Only evaluable participants with a value at Baseline and at Week 52 performed up to 30 days after initiating OL MET or at Week 76 performed up to 30 days after stopping OL MET for the parameter of interest were analyzed.

Volumetric (v)BMD (measured in milligrams per centimeters cubed \[mg/cm\^3\]) was measured by QCT. vBMD is the 3-dimensional density of a region of bone. Cortical bone is dense bone. Trabecular bone is spongy bone. Integral bone is the sum of cortical and trabecular bone measurements. Cortical thickness is the width of the cortical shell. Percent change from Baseline was calculated as (vBMD at Week 52+30 days (or Week 76+30 days) minus vBMD at baseline)/vBMD at Baseline x 100% and was assessed by ANCOVA with terms for treatment, baseline value, prior therapy, and region.

Outcome measures

Outcome measures
Measure	Rosiglitazone in DB Period; Metformin in OL Period n=32 Participants Rosiglitazone (RSG) initiated at a total daily dose of 4 milligrams (mg) in the 52-week DB Period. RSG could be uptitrated to a total daily dose of 8 mg at Week 4. At Week 52, all participants were switched to open-label (OL) Metformin (MET) therapy for 24 weeks during the follow-up phase; all participants were force-titrated from 1000 mg/day to 2000 mg/day over a 4-week period. However, participants could be down-titrated to alleviate any MET-related tolerability issues.	Metformin in DB Period; Metformin in OL Period n=35 Participants Metformin (MET) initiated at a total daily dose of 1000 mg in the 52-week DB Period. MET could be uptitrated to 1500 mg/day at Week 2 and to 2000 mg/day at Week 4. At Week 52, all participants were switched to open-label MET therapy for 24 weeks during the follow-up phase; all participants were force-titrated from 1000 mg/day to 2000 mg/day over a 4-week period. However, participants could be down-titrated to alleviate any MET-related tolerability issues.
Adjusted Percent Change From Baseline in Total Hip (TH) Integral, TH Trabecular, and TH Cortical vBMD Via QCT at Week 52 + 30 Days and at Week 76 + 30 Days Week 52 + 30 days; Integral, n=32, 35	-3.60 percent change Standard Error 0.587	0.99 percent change Standard Error 0.645
Adjusted Percent Change From Baseline in Total Hip (TH) Integral, TH Trabecular, and TH Cortical vBMD Via QCT at Week 52 + 30 Days and at Week 76 + 30 Days Week 52 + 30 days; Trabecular, n=32, 35	-3.63 percent change Standard Error 1.243	0.21 percent change Standard Error 1.376
Adjusted Percent Change From Baseline in Total Hip (TH) Integral, TH Trabecular, and TH Cortical vBMD Via QCT at Week 52 + 30 Days and at Week 76 + 30 Days Week 52 + 30 days; Cortical, n=32, 35	-0.54 percent change Standard Error 0.537	0.52 percent change Standard Error 0.603
Adjusted Percent Change From Baseline in Total Hip (TH) Integral, TH Trabecular, and TH Cortical vBMD Via QCT at Week 52 + 30 Days and at Week 76 + 30 Days Week 76 + 30 days; Integral, n=31, 30	-1.70 percent change Standard Error 0.657	0.85 percent change Standard Error 0.786
Adjusted Percent Change From Baseline in Total Hip (TH) Integral, TH Trabecular, and TH Cortical vBMD Via QCT at Week 52 + 30 Days and at Week 76 + 30 Days Week 76 + 30 days; Trabecular, n=31, 30	-2.66 percent change Standard Error 1.211	0.70 percent change Standard Error 1.445
Adjusted Percent Change From Baseline in Total Hip (TH) Integral, TH Trabecular, and TH Cortical vBMD Via QCT at Week 52 + 30 Days and at Week 76 + 30 Days Week 76 + 30 days; Cortical, n=31, 30	0.23 percent change Standard Error 0.421	0.50 percent change Standard Error 0.518

POST_HOC outcome

Timeframe: Week 52 + 30 days and Week 76 + 30 days

Population: Safety Population, QCT subset. Only evaluable participants with a value at Week 52 performed up to 30 days after initiating OL MET or at Week 76 performed up to 30 days after stopping OL MET for the parameter of interest were analyzed.

Volumetric (v)BMD (measured in milligrams per centimeters cubed \[mg/cm\^3\]) was measured by QCT. vBMD is the 3-dimensional density of a region of bone. Cortical bone is dense bone. Trabecular bone is spongy bone. Integral bone is the sum of cortical and trabecular bone measurements. Cortical thickness is the width of the cortical shell. Percent change from Week 52 + 30 days was calculated as (vBMD at Week 76 + 30 days minus vBMD at Week 52 + 30 days)/ vBMD at Week 52 + 30 days x 100% and was assessed by an ANCOVA with terms for treatment, baseline value, prior therapy, and region.

Outcome measures

Outcome measures
Measure	Rosiglitazone in DB Period; Metformin in OL Period n=30 Participants Rosiglitazone (RSG) initiated at a total daily dose of 4 milligrams (mg) in the 52-week DB Period. RSG could be uptitrated to a total daily dose of 8 mg at Week 4. At Week 52, all participants were switched to open-label (OL) Metformin (MET) therapy for 24 weeks during the follow-up phase; all participants were force-titrated from 1000 mg/day to 2000 mg/day over a 4-week period. However, participants could be down-titrated to alleviate any MET-related tolerability issues.	Metformin in DB Period; Metformin in OL Period n=30 Participants Metformin (MET) initiated at a total daily dose of 1000 mg in the 52-week DB Period. MET could be uptitrated to 1500 mg/day at Week 2 and to 2000 mg/day at Week 4. At Week 52, all participants were switched to open-label MET therapy for 24 weeks during the follow-up phase; all participants were force-titrated from 1000 mg/day to 2000 mg/day over a 4-week period. However, participants could be down-titrated to alleviate any MET-related tolerability issues.
Adjusted Percent Change in Total Hip (TH) Integral, TH Trabecular, and TH Cortical vBMD Via QCT From Week 52+30 Days to Week 76 + 30 Days Integral	2.24 percent change Standard Error 0.483	-0.20 percent change Standard Error 0.5746
Adjusted Percent Change in Total Hip (TH) Integral, TH Trabecular, and TH Cortical vBMD Via QCT From Week 52+30 Days to Week 76 + 30 Days Trabecular	0.90 percent change Standard Error 1.252	1.15 percent change Standard Error 1.491
Adjusted Percent Change in Total Hip (TH) Integral, TH Trabecular, and TH Cortical vBMD Via QCT From Week 52+30 Days to Week 76 + 30 Days Cortical	0.94 percent change Standard Error 0.449	-0.06 percent change Standard Error 0.548

POST_HOC outcome

Timeframe: Baseline, Week 52 + 30 days, and Week 76 + 30 days

Population: Safety Population, QCT subset. Only evaluable participants with a value at Baseline and at Week 52 performed up to 30 days after initiating OL MET or at Week 76 performed up to 30 days after stopping OL MET for the parameter of interest were analyzed.

vBMD (measured in milligrams per centimeters cubed \[mg/cm\^3\]) was measured by QCT. Percent change from Baseline at Week 52 + 30 days or Week 76 + 30 days was calculated as (vBMD at Week 52 + 30 days (orWeek 76 + 30 days) minus vBMD at baseline)/vBMD at Baseline x 100% and was assessed by an analysis of covariance (ANCOVA) with terms for treatment, baseline value, prior therapy, and region.

Outcome measures

Outcome measures
Measure	Rosiglitazone in DB Period; Metformin in OL Period n=32 Participants Rosiglitazone (RSG) initiated at a total daily dose of 4 milligrams (mg) in the 52-week DB Period. RSG could be uptitrated to a total daily dose of 8 mg at Week 4. At Week 52, all participants were switched to open-label (OL) Metformin (MET) therapy for 24 weeks during the follow-up phase; all participants were force-titrated from 1000 mg/day to 2000 mg/day over a 4-week period. However, participants could be down-titrated to alleviate any MET-related tolerability issues.	Metformin in DB Period; Metformin in OL Period n=35 Participants Metformin (MET) initiated at a total daily dose of 1000 mg in the 52-week DB Period. MET could be uptitrated to 1500 mg/day at Week 2 and to 2000 mg/day at Week 4. At Week 52, all participants were switched to open-label MET therapy for 24 weeks during the follow-up phase; all participants were force-titrated from 1000 mg/day to 2000 mg/day over a 4-week period. However, participants could be down-titrated to alleviate any MET-related tolerability issues.
Adjusted Percent Change From Baseline in Femoral Neck (FN) Integral, FN Trabecular, and FN Cortical vBMD Via QCT at Week 52 + 30 Days and Week 76 + 30 Days Week 52 + 30 days, Integral, n=32, 35	-3.72 percent change Standard Error 1.097	0.58 percent change Standard Error 1.208
Adjusted Percent Change From Baseline in Femoral Neck (FN) Integral, FN Trabecular, and FN Cortical vBMD Via QCT at Week 52 + 30 Days and Week 76 + 30 Days Week 52 + 30 days, Trabecular, n=32, 35	-1.83 percent change Standard Error 1.695	0.91 percent change Standard Error 1.867
Adjusted Percent Change From Baseline in Femoral Neck (FN) Integral, FN Trabecular, and FN Cortical vBMD Via QCT at Week 52 + 30 Days and Week 76 + 30 Days Week 52 + 30 days, Cortical, n=32, 35	-1.00 percent change Standard Error 0.735	-0.20 percent change Standard Error 0.819
Adjusted Percent Change From Baseline in Femoral Neck (FN) Integral, FN Trabecular, and FN Cortical vBMD Via QCT at Week 52 + 30 Days and Week 76 + 30 Days Week 76 + 30 days, Integral, n=31, 30	-2.13 percent change Standard Error 0.946	-0.61 percent change Standard Error 1.141
Adjusted Percent Change From Baseline in Femoral Neck (FN) Integral, FN Trabecular, and FN Cortical vBMD Via QCT at Week 52 + 30 Days and Week 76 + 30 Days Week 76 + 30 days, Trabecular, n=31, 30	-1.05 percent change Standard Error 1.798	2.27 percent change Standard Error 2.141
Adjusted Percent Change From Baseline in Femoral Neck (FN) Integral, FN Trabecular, and FN Cortical vBMD Via QCT at Week 52 + 30 Days and Week 76 + 30 Days Week 76 + 30 days, Cortical, n=31, 30	-0.46 percent change Standard Error 0.599	-1.60 percent change Standard Error 0.723

POST_HOC outcome

Timeframe: Week 52 + 30 days and Week 76 + 30 days

Population: Safety Population, QCT subset. Only evaluable participants with a value at Week 52 performed up to 30 days after initiating OL MET or at Week 76 performed up to 30 days after stopping OL MET for the parameter of interest were analyzed.

vBMD (measured in milligrams per centimeters cubed \[mg/cm\^3\]) was measured by QCT. Percent change from Week 52 + 30 days to Week 76 + 30 days was calculated as (vBMD at Week 76 + 30 days minus vBMD at Week 52 + 30 days)/vBMD at Week 52 + 30 days x 100% and was assessed by an analysis of covariance (ANCOVA) with terms for treatment, baseline value, prior therapy, and region.

Outcome measures

Outcome measures
Measure	Rosiglitazone in DB Period; Metformin in OL Period n=30 Participants Rosiglitazone (RSG) initiated at a total daily dose of 4 milligrams (mg) in the 52-week DB Period. RSG could be uptitrated to a total daily dose of 8 mg at Week 4. At Week 52, all participants were switched to open-label (OL) Metformin (MET) therapy for 24 weeks during the follow-up phase; all participants were force-titrated from 1000 mg/day to 2000 mg/day over a 4-week period. However, participants could be down-titrated to alleviate any MET-related tolerability issues.	Metformin in DB Period; Metformin in OL Period n=30 Participants Metformin (MET) initiated at a total daily dose of 1000 mg in the 52-week DB Period. MET could be uptitrated to 1500 mg/day at Week 2 and to 2000 mg/day at Week 4. At Week 52, all participants were switched to open-label MET therapy for 24 weeks during the follow-up phase; all participants were force-titrated from 1000 mg/day to 2000 mg/day over a 4-week period. However, participants could be down-titrated to alleviate any MET-related tolerability issues.
Adjusted Percent Change in Femoral Neck (FN) Integral, FN Trabecular, and FN Cortical vBMD Via QCT From Week 52+30 Days to Week 76 + 30 Days Integral	2.21 percent change Standard Error 0.871	-1.37 percent change Standard Error 1.040
Adjusted Percent Change in Femoral Neck (FN) Integral, FN Trabecular, and FN Cortical vBMD Via QCT From Week 52+30 Days to Week 76 + 30 Days Trabecular	0.27 percent change Standard Error 1.721	2.21 percent change Standard Error 2.044
Adjusted Percent Change in Femoral Neck (FN) Integral, FN Trabecular, and FN Cortical vBMD Via QCT From Week 52+30 Days to Week 76 + 30 Days Cortical	1.03 percent change Standard Error 0.774	-1.30 percent change Standard Error 0.929

POST_HOC outcome

Timeframe: Baseline, Week 52 + 30 days, and Week 76 + 30 days

Population: Safety Population, QCT subset. Only evaluable participants with a value at Baseline and at Week 52 performed up to 30 days after initiating OL MET or at Week 76 performed up to 30 days after stopping OL MET for the parameter of interest were analyzed.

vBMD (measured in milligrams per centimeters cubed \[mg/cm\^3\]) was measured by QCT. Percent change from Baseline at Week 52 + 30 days or Week 76 + 30 days was calculated as (vBMD at Week 52 + 30 days (or Week 76 + 30 days) minus vBMD at baseline)/vBMD at Baseline x 100% and was assessed by an analysis of covariance (ANCOVA) with terms for treatment, baseline value, prior therapy, and region.

Outcome measures

Outcome measures
Measure	Rosiglitazone in DB Period; Metformin in OL Period n=32 Participants Rosiglitazone (RSG) initiated at a total daily dose of 4 milligrams (mg) in the 52-week DB Period. RSG could be uptitrated to a total daily dose of 8 mg at Week 4. At Week 52, all participants were switched to open-label (OL) Metformin (MET) therapy for 24 weeks during the follow-up phase; all participants were force-titrated from 1000 mg/day to 2000 mg/day over a 4-week period. However, participants could be down-titrated to alleviate any MET-related tolerability issues.	Metformin in DB Period; Metformin in OL Period n=35 Participants Metformin (MET) initiated at a total daily dose of 1000 mg in the 52-week DB Period. MET could be uptitrated to 1500 mg/day at Week 2 and to 2000 mg/day at Week 4. At Week 52, all participants were switched to open-label MET therapy for 24 weeks during the follow-up phase; all participants were force-titrated from 1000 mg/day to 2000 mg/day over a 4-week period. However, participants could be down-titrated to alleviate any MET-related tolerability issues.
Adjusted Percent Change From Baseline in Trochanter Integral, Trochanter Trabecular, and Trochanter Cortical vBMD Via QCT at Week 52 + 30 Days and Week 76 + 30 Days Week 52 + 30 days, Integral, n=32, 35	-4.80 percent change Standard Error 0.666	0.01 percent change Standard Error 0.730
Adjusted Percent Change From Baseline in Trochanter Integral, Trochanter Trabecular, and Trochanter Cortical vBMD Via QCT at Week 52 + 30 Days and Week 76 + 30 Days Week 52 + 30 days, Trabecular, n=32, 35	-3.43 percent change Standard Error 1.157	0.67 percent change Standard Error 1.275
Adjusted Percent Change From Baseline in Trochanter Integral, Trochanter Trabecular, and Trochanter Cortical vBMD Via QCT at Week 52 + 30 Days and Week 76 + 30 Days Week 52 + 30 days, Cortical, n=32, 35	-1.26 percent change Standard Error 0.490	-0.18 percent change Standard Error 0.540
Adjusted Percent Change From Baseline in Trochanter Integral, Trochanter Trabecular, and Trochanter Cortical vBMD Via QCT at Week 52 + 30 Days and Week 76 + 30 Days Week 76 + 30 days, Integral, n=31, 30	-2.88 percent change Standard Error 0.748	-0.93 percent change Standard Error 0.889
Adjusted Percent Change From Baseline in Trochanter Integral, Trochanter Trabecular, and Trochanter Cortical vBMD Via QCT at Week 52 + 30 Days and Week 76 + 30 Days Week 76 + 30 days, Trabecular, n=31, 30	-2.42 percent change Standard Error 1.085	0.92 percent change Standard Error 1.293
Adjusted Percent Change From Baseline in Trochanter Integral, Trochanter Trabecular, and Trochanter Cortical vBMD Via QCT at Week 52 + 30 Days and Week 76 + 30 Days Week 76 + 30 days, Cortical, n=31, 30	-0.49 percent change Standard Error 0.384	-0.64 percent change Standard Error 0.462

POST_HOC outcome

Timeframe: Week 52 + 30 days and Week 76 + 30 days

Population: Safety Population, QCT subset. Only evaluable participants with a value at Week 52 performed up to 30 days after initiating OL MET or at Week 76 performed up to 30 days after stopping OL MET for the parameter of interest were analyzed.

vBMD (measured in milligrams per centimeters cubed \[mg/cm\^3\]) was measured by QCT. Percent change from Week 52 + 30 days to Week 76 + 30 days was calculated as (vBMD at Week 76 + 30 days minus vBMD at Week 52 + 30 days)/vBMD at Week 52 + 30 days x 100% and was assessed by an analysis of covariance (ANCOVA) with terms for treatment, baseline value, prior therapy, and region.

Outcome measures

Outcome measures
Measure	Rosiglitazone in DB Period; Metformin in OL Period n=30 Participants Rosiglitazone (RSG) initiated at a total daily dose of 4 milligrams (mg) in the 52-week DB Period. RSG could be uptitrated to a total daily dose of 8 mg at Week 4. At Week 52, all participants were switched to open-label (OL) Metformin (MET) therapy for 24 weeks during the follow-up phase; all participants were force-titrated from 1000 mg/day to 2000 mg/day over a 4-week period. However, participants could be down-titrated to alleviate any MET-related tolerability issues.	Metformin in DB Period; Metformin in OL Period n=30 Participants Metformin (MET) initiated at a total daily dose of 1000 mg in the 52-week DB Period. MET could be uptitrated to 1500 mg/day at Week 2 and to 2000 mg/day at Week 4. At Week 52, all participants were switched to open-label MET therapy for 24 weeks during the follow-up phase; all participants were force-titrated from 1000 mg/day to 2000 mg/day over a 4-week period. However, participants could be down-titrated to alleviate any MET-related tolerability issues.
Adjusted Percent Change in Trochanter Integral, Trochanter Trabecular, and Trochanter Cortical vBMD Via QCT From Week 52+30 Days to Week 76 + 30 Days percent change	2.22 percent change Standard Error 0.506	-0.90 percent change Standard Error 0.600
Adjusted Percent Change in Trochanter Integral, Trochanter Trabecular, and Trochanter Cortical vBMD Via QCT From Week 52+30 Days to Week 76 + 30 Days Trabecular	1.07 percent change Standard Error 1.138	0.95 percent change Standard Error 1.353
Adjusted Percent Change in Trochanter Integral, Trochanter Trabecular, and Trochanter Cortical vBMD Via QCT From Week 52+30 Days to Week 76 + 30 Days Cortical	0.78 percent change Standard Error 0.396	-0.65 percent change Standard Error 0.474

POST_HOC outcome

Timeframe: Baseline, Week 52 + 30 days, and Week 76 + 30 days

Population: Safety Population, QCT subset. Only evaluable participants with a value at Baseline and at Week 52 performed up to 30 days after initiating OL MET or at Week 76 performed up to 30 days after stopping OL MET for the parameter of interest were analyzed.

vBMD (measured in milligrams per centimeters cubed \[mg/cm\^3\]) was measured by QCT. Percent change from Baseline at Week 52 + 30 days or Week 76 + 30 days was calculated as (vBMD at Week 52 + 30 days (or Week 76 + 30 days) minus vBMD at baseline)/vBMD at Baseline x 100% and was assessed by an analysis of covariance (ANCOVA) with terms for treatment, baseline value, prior therapy, and region.

Outcome measures

Outcome measures
Measure	Rosiglitazone in DB Period; Metformin in OL Period n=32 Participants Rosiglitazone (RSG) initiated at a total daily dose of 4 milligrams (mg) in the 52-week DB Period. RSG could be uptitrated to a total daily dose of 8 mg at Week 4. At Week 52, all participants were switched to open-label (OL) Metformin (MET) therapy for 24 weeks during the follow-up phase; all participants were force-titrated from 1000 mg/day to 2000 mg/day over a 4-week period. However, participants could be down-titrated to alleviate any MET-related tolerability issues.	Metformin in DB Period; Metformin in OL Period n=35 Participants Metformin (MET) initiated at a total daily dose of 1000 mg in the 52-week DB Period. MET could be uptitrated to 1500 mg/day at Week 2 and to 2000 mg/day at Week 4. At Week 52, all participants were switched to open-label MET therapy for 24 weeks during the follow-up phase; all participants were force-titrated from 1000 mg/day to 2000 mg/day over a 4-week period. However, participants could be down-titrated to alleviate any MET-related tolerability issues.
Adjusted Percent Change From Baseline in Intertrochanter Integral, Intertrochanter Trabecular, and Intertrochanter Cortical vBMD Via QCT at Week 52 + 30 Days and Week 76 + 30 Days Week 52 + 30 days, Integral, n=32, 35	-3.47 percent change Standard Error 0.621	2.18 percent change Standard Error 0.683
Adjusted Percent Change From Baseline in Intertrochanter Integral, Intertrochanter Trabecular, and Intertrochanter Cortical vBMD Via QCT at Week 52 + 30 Days and Week 76 + 30 Days Week 52 + 30 days, Trabecular, n=32, 35	-4.26 percent change Standard Error 1.341	-0.22 percent change Standard Error 1.485
Adjusted Percent Change From Baseline in Intertrochanter Integral, Intertrochanter Trabecular, and Intertrochanter Cortical vBMD Via QCT at Week 52 + 30 Days and Week 76 + 30 Days Week 52 + 30 days, Cortical, n=32, 35	-0.76 percent change Standard Error 0.568	0.99 percent change Standard Error 0.631
Adjusted Percent Change From Baseline in Intertrochanter Integral, Intertrochanter Trabecular, and Intertrochanter Cortical vBMD Via QCT at Week 52 + 30 Days and Week 76 + 30 Days Week 76 + 30 days, Integral, n=31, 30	-0.92 percent change Standard Error 0.746	1.88 percent change Standard Error 0.895
Adjusted Percent Change From Baseline in Intertrochanter Integral, Intertrochanter Trabecular, and Intertrochanter Cortical vBMD Via QCT at Week 52 + 30 Days and Week 76 + 30 Days Week 76 + 30 days, Trabecular, n=31, 30	-3.09 percent change Standard Error 1.278	0.27 percent change Standard Error 1.525
Adjusted Percent Change From Baseline in Intertrochanter Integral, Intertrochanter Trabecular, and Intertrochanter Cortical vBMD Via QCT at Week 52 + 30 Days and Week 76 + 30 Days Week 76 + 30 days, Cortical, n=31, 30	0.41 percent change Standard Error 0.472	0.79 percent change Standard Error 0.573

POST_HOC outcome

Timeframe: Week 52 + 30 days and Week 76 + 30 days

Population: Safety Population, QCT subset. Only evaluable participants with a value at Week 52 performed up to 30 days after initiating OL MET or at Week 76 performed up to 30 days after stopping OL MET for the parameter of interest were analyzed.

vBMD (measured in milligrams per centimeters cubed \[mg/cm\^3\]) was measured by QCT. Percent change from Week 52 + 30 days to Week 76 + 30 days was calculated as (vBMD at Week 76 + 30 days minus vBMD at Week 52 + 30 days)/vBMD at Week 52 + 30 days x 100% and was assessed by an analysis of covariance (ANCOVA) with terms for treatment, baseline value, prior therapy, and region.

Outcome measures

Outcome measures
Measure	Rosiglitazone in DB Period; Metformin in OL Period n=30 Participants Rosiglitazone (RSG) initiated at a total daily dose of 4 milligrams (mg) in the 52-week DB Period. RSG could be uptitrated to a total daily dose of 8 mg at Week 4. At Week 52, all participants were switched to open-label (OL) Metformin (MET) therapy for 24 weeks during the follow-up phase; all participants were force-titrated from 1000 mg/day to 2000 mg/day over a 4-week period. However, participants could be down-titrated to alleviate any MET-related tolerability issues.	Metformin in DB Period; Metformin in OL Period n=30 Participants Metformin (MET) initiated at a total daily dose of 1000 mg in the 52-week DB Period. MET could be uptitrated to 1500 mg/day at Week 2 and to 2000 mg/day at Week 4. At Week 52, all participants were switched to open-label MET therapy for 24 weeks during the follow-up phase; all participants were force-titrated from 1000 mg/day to 2000 mg/day over a 4-week period. However, participants could be down-titrated to alleviate any MET-related tolerability issues.
Adjusted Percent Change in Intertrochanter Integral, Intertrochanter Trabecular, and Intertrochanter Cortical vBMD Via QCT From Week 52+30 Days to Week 76 + 30 Days percent change	2.83 percent change Standard Error 0.563	-0.46 percent change Standard Error 0.671
Adjusted Percent Change in Intertrochanter Integral, Intertrochanter Trabecular, and Intertrochanter Cortical vBMD Via QCT From Week 52+30 Days to Week 76 + 30 Days Trabecular	1.16 percent change Standard Error 1.298	1.21 percent change Standard Error 1.545
Adjusted Percent Change in Intertrochanter Integral, Intertrochanter Trabecular, and Intertrochanter Cortical vBMD Via QCT From Week 52+30 Days to Week 76 + 30 Days Cortical	1.29 percent change Standard Error 0.479	-0.27 percent change Standard Error 0.577

POST_HOC outcome

Timeframe: Baseline, Week 52 + 30 days, and Week 76 + 30 days

Population: Safety Population, QCT subset. Only evaluable participants with a value at Baseline and at Week 52 performed up to 30 days after initiating OL MET or at Week 76 performed up to 30 days after stopping OL MET for the parameter of interest were analyzed.

BMD (measured in milligrams per centimeters cubed \[mg/cm\^3\]) was measured by QCT. Percent change from Baseline at Week 52 + 30 days or Week 76 + 30 days was calculated as (vBMD at Week 52 + 30 days (orWeek 76 + 30 days) minus vBMD at baseline)/vBMD at Baseline x 100% and was assessed by an analysis of covariance (ANCOVA) with terms for treatment, baseline value, prior therapy, and region.

Outcome measures

Outcome measures
Measure	Rosiglitazone in DB Period; Metformin in OL Period n=32 Participants Rosiglitazone (RSG) initiated at a total daily dose of 4 milligrams (mg) in the 52-week DB Period. RSG could be uptitrated to a total daily dose of 8 mg at Week 4. At Week 52, all participants were switched to open-label (OL) Metformin (MET) therapy for 24 weeks during the follow-up phase; all participants were force-titrated from 1000 mg/day to 2000 mg/day over a 4-week period. However, participants could be down-titrated to alleviate any MET-related tolerability issues.	Metformin in DB Period; Metformin in OL Period n=35 Participants Metformin (MET) initiated at a total daily dose of 1000 mg in the 52-week DB Period. MET could be uptitrated to 1500 mg/day at Week 2 and to 2000 mg/day at Week 4. At Week 52, all participants were switched to open-label MET therapy for 24 weeks during the follow-up phase; all participants were force-titrated from 1000 mg/day to 2000 mg/day over a 4-week period. However, participants could be down-titrated to alleviate any MET-related tolerability issues.
Adjusted Percent Change From Baseline in Vertebral Trabecular vBMD Via QCT at Week 52 + 30 Days and Week 76 + 30 Days Week 52 + 30 days, n=32, 35	-6.71 percent change Standard Error 1.454	-1.72 percent change Standard Error 1.601
Adjusted Percent Change From Baseline in Vertebral Trabecular vBMD Via QCT at Week 52 + 30 Days and Week 76 + 30 Days Week 76 + 30 days, n=31, 30	-5.15 percent change Standard Error 1.121	-3.91 percent change Standard Error 1.337

POST_HOC outcome

Timeframe: Week 52 + 30 days and Week 76 + 30 days

Population: Safety Population, QCT subset. Only evaluable participants with a value at Week 52 performed up to 30 days after initiating OL MET or at Week 76 performed up to 30 days after stopping OL MET for the parameter of interest were analyzed.

BMD (measured in milligrams per centimeters cubed \[mg/cm\^3\]) was measured by QCT. Percent change from Week 52 + 30 days to Week 76 + 30 days was calculated as (vBMD at Week 76 + 30 days minus vBMD at Week 52 + 30 days)/vBMD at Week 52 + 30 days x 100% and was assessed by an analysis of covariance (ANCOVA) with terms for treatment, baseline value, prior therapy, and region.

Outcome measures

Outcome measures
Measure	Rosiglitazone in DB Period; Metformin in OL Period n=30 Participants Rosiglitazone (RSG) initiated at a total daily dose of 4 milligrams (mg) in the 52-week DB Period. RSG could be uptitrated to a total daily dose of 8 mg at Week 4. At Week 52, all participants were switched to open-label (OL) Metformin (MET) therapy for 24 weeks during the follow-up phase; all participants were force-titrated from 1000 mg/day to 2000 mg/day over a 4-week period. However, participants could be down-titrated to alleviate any MET-related tolerability issues.	Metformin in DB Period; Metformin in OL Period n=30 Participants Metformin (MET) initiated at a total daily dose of 1000 mg in the 52-week DB Period. MET could be uptitrated to 1500 mg/day at Week 2 and to 2000 mg/day at Week 4. At Week 52, all participants were switched to open-label MET therapy for 24 weeks during the follow-up phase; all participants were force-titrated from 1000 mg/day to 2000 mg/day over a 4-week period. However, participants could be down-titrated to alleviate any MET-related tolerability issues.
Adjusted Percent Change in Vertebral Trabecular vBMD Via QCT From Week 52+30 Days to Week 76 + 30 Days	3.53 percent change Standard Error 1.454	-2.11 percent change Standard Error 1.727

POST_HOC outcome

Timeframe: Baseline, Week 52 + 30 days, and Week 76 + 30 days

Population: Safety Population, QCT subset. Only evaluable participants with a value at Baseline and at Week 52 performed up to 30 days after initiating OL MET or Week 76 performed up to 30 days after stopping OL MET for the parameter of interest were analyzed.

vBMD (measured in milligrams per centimeters cubed \[mg/cm\^3\]) was measured by QCT. Percent change from Baseline at Week 52 + 30 days orWeek 76 + 30 days was calculated as (vBMD at Week 52 + 30 days (or Week 76 + 30 days) minus vBMD at baseline)/vBMD at Baseline x 100% and was assessed by an analysis of covariance (ANCOVA) with terms for treatment, baseline value, prior therpay, and region. Supero-posterior is the upper and back section of the FN.

Outcome measures

Outcome measures
Measure	Rosiglitazone in DB Period; Metformin in OL Period n=32 Participants Rosiglitazone (RSG) initiated at a total daily dose of 4 milligrams (mg) in the 52-week DB Period. RSG could be uptitrated to a total daily dose of 8 mg at Week 4. At Week 52, all participants were switched to open-label (OL) Metformin (MET) therapy for 24 weeks during the follow-up phase; all participants were force-titrated from 1000 mg/day to 2000 mg/day over a 4-week period. However, participants could be down-titrated to alleviate any MET-related tolerability issues.	Metformin in DB Period; Metformin in OL Period n=35 Participants Metformin (MET) initiated at a total daily dose of 1000 mg in the 52-week DB Period. MET could be uptitrated to 1500 mg/day at Week 2 and to 2000 mg/day at Week 4. At Week 52, all participants were switched to open-label MET therapy for 24 weeks during the follow-up phase; all participants were force-titrated from 1000 mg/day to 2000 mg/day over a 4-week period. However, participants could be down-titrated to alleviate any MET-related tolerability issues.
Adjusted Percent Change From Baseline in Femoral Neck (FN) Supero-posterior Integral, Trabecular, and Cortical vBMD Via QCT at Week 52 + 30 Days and Week 76 + 30 Days Week 52 + 30 days, Integral, n=32, 35	-10.26 percent change Standard Error 2.194	-0.03 percent change Standard Error 2.417
Adjusted Percent Change From Baseline in Femoral Neck (FN) Supero-posterior Integral, Trabecular, and Cortical vBMD Via QCT at Week 52 + 30 Days and Week 76 + 30 Days Week 52 + 30 days, Trabecular, n=32, 35	2.77 percent change Standard Error 5.848	5.57 percent change Standard Error 6.420
Adjusted Percent Change From Baseline in Femoral Neck (FN) Supero-posterior Integral, Trabecular, and Cortical vBMD Via QCT at Week 52 + 30 Days and Week 76 + 30 Days Week 52 + 30 days, Cortical, n=32, 35	-3.76 percent change Standard Error 0.836	-0.66 percent change Standard Error 0.922
Adjusted Percent Change From Baseline in Femoral Neck (FN) Supero-posterior Integral, Trabecular, and Cortical vBMD Via QCT at Week 52 + 30 Days and Week 76 + 30 Days Week 76 + 30 days, Integral, n=31, 30	-4.21 percent change Standard Error 2.094	1.07 percent change Standard Error 2.508
Adjusted Percent Change From Baseline in Femoral Neck (FN) Supero-posterior Integral, Trabecular, and Cortical vBMD Via QCT at Week 52 + 30 Days and Week 76 + 30 Days Week 76 + 30 days, Trabecular, n=31, 30	2.37 percent change Standard Error 7.040	10.24 percent change Standard Error 8.362
Adjusted Percent Change From Baseline in Femoral Neck (FN) Supero-posterior Integral, Trabecular, and Cortical vBMD Via QCT at Week 52 + 30 Days and Week 76 + 30 Days Week 76 + 30 days, Cortical, n=31, 30	-1.65 percent change Standard Error 0.730	-1.30 percent change Standard Error 0.877

POST_HOC outcome

Timeframe: Baseline and Week 76 + 30 days

Population: Safety Population, QCT subset. Only evaluable participants with a value at Baseline and at Week 76 performed up to 30 days after stopping OL MET for the parameter of interest were analyzed.

vBMD was measured by QCT. Change from Baseline at Week 76 + 30 days was calculated as vBMD at Week 76 + 30 days minus vBMD at baseline and was assessed by an analysis of covariance (ANCOVA) with terms for treatment, baseline value, prior therapy, and region. Supero-posterior is the upper and back section of the FN.

Outcome measures

Outcome measures
Measure	Rosiglitazone in DB Period; Metformin in OL Period n=31 Participants Rosiglitazone (RSG) initiated at a total daily dose of 4 milligrams (mg) in the 52-week DB Period. RSG could be uptitrated to a total daily dose of 8 mg at Week 4. At Week 52, all participants were switched to open-label (OL) Metformin (MET) therapy for 24 weeks during the follow-up phase; all participants were force-titrated from 1000 mg/day to 2000 mg/day over a 4-week period. However, participants could be down-titrated to alleviate any MET-related tolerability issues.	Metformin in DB Period; Metformin in OL Period n=30 Participants Metformin (MET) initiated at a total daily dose of 1000 mg in the 52-week DB Period. MET could be uptitrated to 1500 mg/day at Week 2 and to 2000 mg/day at Week 4. At Week 52, all participants were switched to open-label MET therapy for 24 weeks during the follow-up phase; all participants were force-titrated from 1000 mg/day to 2000 mg/day over a 4-week period. However, participants could be down-titrated to alleviate any MET-related tolerability issues.
Adjusted Change From Baseline in Femoral Neck (FN) Supero-posterior and Cortical vBMD Via QCT at Week 76 + 30 Days	-8.007 mg/cm^3 Standard Error 3.4199	-7.006 mg/cm^3 Standard Error 4.1114

POST_HOC outcome

Timeframe: Week 52 + 30 days and Week 76 + 30 days

Population: Safety Population, QCT subset. Only evaluable participants with a value at Week 52 performed up to 30 days after initiating OL MET or at Week 76 performed up to 30 days after stopping OL MET for the parameter of interest were analyzed.

vBMD (measured in milligrams per centimeters cubed \[mg/cm\^3\]) was measured by QCT. Percent change from Week 52 + 30 days to Week 76 + 30 days was calculated as (vBMD at Week 76 + 30 days minus vBMD at Week 52 + 30 days)/vBMD at Week 52 + 30 days x 100% and was assessed by an analysis of covariance (ANCOVA) with terms for treatment, baseline value, prior therpay, and region. Supero-posterior is the upper and back section of the FN.

Outcome measures

Outcome measures
Measure	Rosiglitazone in DB Period; Metformin in OL Period n=30 Participants Rosiglitazone (RSG) initiated at a total daily dose of 4 milligrams (mg) in the 52-week DB Period. RSG could be uptitrated to a total daily dose of 8 mg at Week 4. At Week 52, all participants were switched to open-label (OL) Metformin (MET) therapy for 24 weeks during the follow-up phase; all participants were force-titrated from 1000 mg/day to 2000 mg/day over a 4-week period. However, participants could be down-titrated to alleviate any MET-related tolerability issues.	Metformin in DB Period; Metformin in OL Period n=30 Participants Metformin (MET) initiated at a total daily dose of 1000 mg in the 52-week DB Period. MET could be uptitrated to 1500 mg/day at Week 2 and to 2000 mg/day at Week 4. At Week 52, all participants were switched to open-label MET therapy for 24 weeks during the follow-up phase; all participants were force-titrated from 1000 mg/day to 2000 mg/day over a 4-week period. However, participants could be down-titrated to alleviate any MET-related tolerability issues.
Adjusted Percent Change in Femoral Neck (FN) Supero-posterior Integral, Trabecular, and Cortical vBMD Via QCT From Week 52+30 Days to Week 76 + 30 Days Integral	8.29 percent change Standard Error 3.262	0.52 percent change Standard Error 3.884
Adjusted Percent Change in Femoral Neck (FN) Supero-posterior Integral, Trabecular, and Cortical vBMD Via QCT From Week 52+30 Days to Week 76 + 30 Days Trabecular	36.05 percent change Standard Error 31.815	-11.69 percent change Standard Error 37.721
Adjusted Percent Change in Femoral Neck (FN) Supero-posterior Integral, Trabecular, and Cortical vBMD Via QCT From Week 52+30 Days to Week 76 + 30 Days Cortical	2.17 percent change Standard Error 0.944	-0.94 percent change Standard Error 1.129

POST_HOC outcome

Timeframe: Week 52 + 30 days and Week 76 + 30 days

Population: Safety Population, QCT subset. Only evaluable participants with a value at Week 52 performed up to 30 days after initiating OL MET or at Week 76 performed up to 30 days after stopping OL MET for the parameter of interest were analyzed.

vBMD was measured by QCT. Change from Week 52 + 30 days to Week 76 + 30 days was calculated as vBMD at Week 76 + 30 days minus vBMD at Week 52 + 30 days and was assessed by an analysis of covariance (ANCOVA) with terms for treatment, baseline value, prior therpay, and region. Supero-posterior is the upper and back section of the FN.

Outcome measures

Outcome measures
Measure	Rosiglitazone in DB Period; Metformin in OL Period n=30 Participants Rosiglitazone (RSG) initiated at a total daily dose of 4 milligrams (mg) in the 52-week DB Period. RSG could be uptitrated to a total daily dose of 8 mg at Week 4. At Week 52, all participants were switched to open-label (OL) Metformin (MET) therapy for 24 weeks during the follow-up phase; all participants were force-titrated from 1000 mg/day to 2000 mg/day over a 4-week period. However, participants could be down-titrated to alleviate any MET-related tolerability issues.	Metformin in DB Period; Metformin in OL Period n=30 Participants Metformin (MET) initiated at a total daily dose of 1000 mg in the 52-week DB Period. MET could be uptitrated to 1500 mg/day at Week 2 and to 2000 mg/day at Week 4. At Week 52, all participants were switched to open-label MET therapy for 24 weeks during the follow-up phase; all participants were force-titrated from 1000 mg/day to 2000 mg/day over a 4-week period. However, participants could be down-titrated to alleviate any MET-related tolerability issues.
Adjusted Change in Femoral Neck (FN) Supero-posterior Cortical vBMD Via QCT From Week 52 + 30 Days to Week 76 + 30 Days	9.30 mg/cm^3 Standard Error 4.287	-4.92 mg/cm^3 Standard Error 5.130

POST_HOC outcome

Timeframe: Baseline, Week 52 + 30 days, and Week 76 + 30 days

Population: Safety Population, QCT subset. Only evaluable participants with a value at Baseline and at Week 52 performed up to 30 days after initiating OL MET or at Week 76 performed up to 30 days after stopping OL MET for the parameter of interest were analyzed.

Cortical thickness (measured in millimeters) was measured by QCT. Percent change was calculated as (thickness at Week 52 + 30 days (or Week 76 + 30 days) minus thickness at Baseline)/thickness at Baseline x 100%

Outcome measures

Outcome measures
Measure	Rosiglitazone in DB Period; Metformin in OL Period n=32 Participants Rosiglitazone (RSG) initiated at a total daily dose of 4 milligrams (mg) in the 52-week DB Period. RSG could be uptitrated to a total daily dose of 8 mg at Week 4. At Week 52, all participants were switched to open-label (OL) Metformin (MET) therapy for 24 weeks during the follow-up phase; all participants were force-titrated from 1000 mg/day to 2000 mg/day over a 4-week period. However, participants could be down-titrated to alleviate any MET-related tolerability issues.	Metformin in DB Period; Metformin in OL Period n=35 Participants Metformin (MET) initiated at a total daily dose of 1000 mg in the 52-week DB Period. MET could be uptitrated to 1500 mg/day at Week 2 and to 2000 mg/day at Week 4. At Week 52, all participants were switched to open-label MET therapy for 24 weeks during the follow-up phase; all participants were force-titrated from 1000 mg/day to 2000 mg/day over a 4-week period. However, participants could be down-titrated to alleviate any MET-related tolerability issues.
Adjusted Percent Change From Baseline in Femoral Neck (FN) Supero-posterior Cortical Thickness Via QCT at Week 52 + 30 Days and Week 76 + 30 Days Week 52 + 30 days, n=32, 35	-20.48 percent change Standard Error 3.614	1.00 percent change Standard Error 3.986
Adjusted Percent Change From Baseline in Femoral Neck (FN) Supero-posterior Cortical Thickness Via QCT at Week 52 + 30 Days and Week 76 + 30 Days Week 76 + 30 days, n=31,30	-3.52 percent change Standard Error 3.674	-1.50 percent change Standard Error 4.423

POST_HOC outcome

Timeframe: Baseline and Week 76 + 30 days

Population: Safety Population, QCT subset. Only evaluable participants with a value at Baseline and at Week 76 performed up to 30 days after stopping OL MET for the parameter of interest were analyzed.

Cortical thickness was measured by QCT. Change from baseline was calculated as thickness at Week 76 + 30 days minus thickness at Baseline.

Outcome measures

Outcome measures
Measure	Rosiglitazone in DB Period; Metformin in OL Period n=31 Participants Rosiglitazone (RSG) initiated at a total daily dose of 4 milligrams (mg) in the 52-week DB Period. RSG could be uptitrated to a total daily dose of 8 mg at Week 4. At Week 52, all participants were switched to open-label (OL) Metformin (MET) therapy for 24 weeks during the follow-up phase; all participants were force-titrated from 1000 mg/day to 2000 mg/day over a 4-week period. However, participants could be down-titrated to alleviate any MET-related tolerability issues.	Metformin in DB Period; Metformin in OL Period n=30 Participants Metformin (MET) initiated at a total daily dose of 1000 mg in the 52-week DB Period. MET could be uptitrated to 1500 mg/day at Week 2 and to 2000 mg/day at Week 4. At Week 52, all participants were switched to open-label MET therapy for 24 weeks during the follow-up phase; all participants were force-titrated from 1000 mg/day to 2000 mg/day over a 4-week period. However, participants could be down-titrated to alleviate any MET-related tolerability issues.
Adjusted Change From Baseline in Femoral Neck (FN) Supero-posterior Cortical Thickness Via QCT at Week 76 + 30 Days	-0.95 millimeters Standard Error 0.0537	-0.067 millimeters Standard Error 0.0647

POST_HOC outcome

Timeframe: Week 52 + 30 days and Week 76 + 30 days

Population: Safety Population, QCT subset. Only evaluable participants with a value at Week 52 performed up to 30 days after initiating OL MET or at Week 76 performed up to 30 days after stopping OL MET for the parameter of interest were analyzed.

Cortical thickness (measured in millimeters) was measured by QCT. Percent change was calculated as (thickness at Week 76 + 30 days minus thickness at Week 52 + 30 days)/thickness at Week 52 + 30 days x 100%.

Outcome measures

Outcome measures
Measure	Rosiglitazone in DB Period; Metformin in OL Period n=30 Participants Rosiglitazone (RSG) initiated at a total daily dose of 4 milligrams (mg) in the 52-week DB Period. RSG could be uptitrated to a total daily dose of 8 mg at Week 4. At Week 52, all participants were switched to open-label (OL) Metformin (MET) therapy for 24 weeks during the follow-up phase; all participants were force-titrated from 1000 mg/day to 2000 mg/day over a 4-week period. However, participants could be down-titrated to alleviate any MET-related tolerability issues.	Metformin in DB Period; Metformin in OL Period n=30 Participants Metformin (MET) initiated at a total daily dose of 1000 mg in the 52-week DB Period. MET could be uptitrated to 1500 mg/day at Week 2 and to 2000 mg/day at Week 4. At Week 52, all participants were switched to open-label MET therapy for 24 weeks during the follow-up phase; all participants were force-titrated from 1000 mg/day to 2000 mg/day over a 4-week period. However, participants could be down-titrated to alleviate any MET-related tolerability issues.
Adjusted Percent Change in Femoral Neck (FN) Supero-posterior Cortical Thickness Via QCT From Week 52+30 Days to Week 76 + 30 Days	32.42 percent change Standard Error 10.358	-7.80 percent change Standard Error 2.383

POST_HOC outcome

Timeframe: Week 52 + 30 days and Week 76 + 30 days

Population: Safety Population, QCT subset. Only evaluable participants with a value at Week 52 performed up to 30 days after initiating OL MET or at Week 76 performed up to 30 days after stopping OL MET for the parameter of interest were analyzed.

Cortical thickness was measured by QCT. Change was calculated as thickness at Week 76 + 30 days minus thickness at Week 52 + 30 days.

Outcome measures

Outcome measures
Measure	Rosiglitazone in DB Period; Metformin in OL Period n=30 Participants Rosiglitazone (RSG) initiated at a total daily dose of 4 milligrams (mg) in the 52-week DB Period. RSG could be uptitrated to a total daily dose of 8 mg at Week 4. At Week 52, all participants were switched to open-label (OL) Metformin (MET) therapy for 24 weeks during the follow-up phase; all participants were force-titrated from 1000 mg/day to 2000 mg/day over a 4-week period. However, participants could be down-titrated to alleviate any MET-related tolerability issues.	Metformin in DB Period; Metformin in OL Period n=30 Participants Metformin (MET) initiated at a total daily dose of 1000 mg in the 52-week DB Period. MET could be uptitrated to 1500 mg/day at Week 2 and to 2000 mg/day at Week 4. At Week 52, all participants were switched to open-label MET therapy for 24 weeks during the follow-up phase; all participants were force-titrated from 1000 mg/day to 2000 mg/day over a 4-week period. However, participants could be down-titrated to alleviate any MET-related tolerability issues.
Adjusted Change in Femoral Neck (FN) Supero-posterior Cortical Thickness Via QCT From Week 52 + 30 Days to Week 76 + 30 Days	0.18 millimeters Standard Error 0.049	-0.05 millimeters Standard Error 0.059

POST_HOC outcome

Timeframe: Baseline, Week 52 plus 30 days, and Week 76 + 30 days

Population: Safety Population, QCT subset. Only evaluable participants with a value at Baseline and at Week 52 performed up to 30 days after initiating OL MET or at Week 76 performed up to 30 days after stopping OL MET for the parameter of interest were analyzed.

vBMD (measured in milligrams per centimeters cubed \[mg/cm\^3\]) was measured by QCT. Percent change from Baseline at Week 52 + 30 daysor Week 76 + 30 days was calculated as (vBMD at Week 52 + 30 days(or Week 76 + 30 days) minus vBMD at baseline)/vBMD at Baseline x 100% and was assessed by an analysis of covariance (ANCOVA) with terms for treatment, baseline value, prior therapy, and region. Supero-anterior is the upper and front section of the FN.

Outcome measures

Outcome measures
Measure	Rosiglitazone in DB Period; Metformin in OL Period n=32 Participants Rosiglitazone (RSG) initiated at a total daily dose of 4 milligrams (mg) in the 52-week DB Period. RSG could be uptitrated to a total daily dose of 8 mg at Week 4. At Week 52, all participants were switched to open-label (OL) Metformin (MET) therapy for 24 weeks during the follow-up phase; all participants were force-titrated from 1000 mg/day to 2000 mg/day over a 4-week period. However, participants could be down-titrated to alleviate any MET-related tolerability issues.	Metformin in DB Period; Metformin in OL Period n=35 Participants Metformin (MET) initiated at a total daily dose of 1000 mg in the 52-week DB Period. MET could be uptitrated to 1500 mg/day at Week 2 and to 2000 mg/day at Week 4. At Week 52, all participants were switched to open-label MET therapy for 24 weeks during the follow-up phase; all participants were force-titrated from 1000 mg/day to 2000 mg/day over a 4-week period. However, participants could be down-titrated to alleviate any MET-related tolerability issues.
Adjusted Percent Change From Baseline in Femoral Neck (FN) Supero-anterior Integral, Trabecular, and Cortical vBMD Via QCT at Week 52 + 30 Days and Week 76 + 30 Days Week 52 + 30 days, Integral, n=32, 35	-6.56 percent change Standard Error 2.106	-0.58 percent change Standard Error 2.311
Adjusted Percent Change From Baseline in Femoral Neck (FN) Supero-anterior Integral, Trabecular, and Cortical vBMD Via QCT at Week 52 + 30 Days and Week 76 + 30 Days Week 52 + 30 days, Trabecular, n=32, 35	3.59 percent change Standard Error 4.719	2.82 percent change Standard Error 5.180
Adjusted Percent Change From Baseline in Femoral Neck (FN) Supero-anterior Integral, Trabecular, and Cortical vBMD Via QCT at Week 52 + 30 Days and Week 76 + 30 Days Week 52 + 30 days, Cortical, n=32, 35	-1.91 percent change Standard Error 0.901	-0.25 percent change Standard Error 0.977
Adjusted Percent Change From Baseline in Femoral Neck (FN) Supero-anterior Integral, Trabecular, and Cortical vBMD Via QCT at Week 52 + 30 Days and Week 76 + 30 Days Week 76 + 30 days, Integral, n=31, 30	-4.97 percent change Standard Error 2.384	-2.45 percent change Standard Error 2.838
Adjusted Percent Change From Baseline in Femoral Neck (FN) Supero-anterior Integral, Trabecular, and Cortical vBMD Via QCT at Week 52 + 30 Days and Week 76 + 30 Days Week 76 + 30 days, Trabecular, n=31, 30	-0.85 percent change Standard Error 6.050	3.98 percent change Standard Error 7.171
Adjusted Percent Change From Baseline in Femoral Neck (FN) Supero-anterior Integral, Trabecular, and Cortical vBMD Via QCT at Week 52 + 30 Days and Week 76 + 30 Days Week 76 + 30 days, Cortical, n=31, 30	-0.93 percent change Standard Error 0.745	-1.49 percent change Standard Error 0.876

POST_HOC outcome

Timeframe: Baseline and Week 76 + 30 days

Population: Safety Population, QCT subset. Only evaluable participants with a value at Baseline and at Week 76 performed up to 30 days after stopping OL MET for the parameter of interest were analyzed.

vBMD was measured by QCT. Change from Baseline at Week 76 + 30 days was calculated as vBMD at Week 76 + 30 days minus vBMD at baseline and was assessed by an analysis of covariance (ANCOVA) with terms for treatment, baseline value, prior therapy, and region. Supero-anterior is the upper and front section of the FN.

Outcome measures

Outcome measures
Measure	Rosiglitazone in DB Period; Metformin in OL Period n=31 Participants Rosiglitazone (RSG) initiated at a total daily dose of 4 milligrams (mg) in the 52-week DB Period. RSG could be uptitrated to a total daily dose of 8 mg at Week 4. At Week 52, all participants were switched to open-label (OL) Metformin (MET) therapy for 24 weeks during the follow-up phase; all participants were force-titrated from 1000 mg/day to 2000 mg/day over a 4-week period. However, participants could be down-titrated to alleviate any MET-related tolerability issues.	Metformin in DB Period; Metformin in OL Period n=30 Participants Metformin (MET) initiated at a total daily dose of 1000 mg in the 52-week DB Period. MET could be uptitrated to 1500 mg/day at Week 2 and to 2000 mg/day at Week 4. At Week 52, all participants were switched to open-label MET therapy for 24 weeks during the follow-up phase; all participants were force-titrated from 1000 mg/day to 2000 mg/day over a 4-week period. However, participants could be down-titrated to alleviate any MET-related tolerability issues.
Adjusted Change From Baseline in Femoral Neck (FN) Supero-anterior Cortical vBMD Via QCT at Week 76 + 30 Days	-4.555 mg/cm^3 Standard Error 3.5006	-7.553 mg/cm^3 Standard Error 4.1177

POST_HOC outcome

Timeframe: Week 52 + 30 days and Week 76 + 30 days

Population: Safety Population, QCT subset. Only evaluable participants with a value at Week 52 performed up to 30 days after initiating OL MET or at Week 76 performed up to 30 days after stopping OL MET for the parameter of interest were analyzed.

vBMD (measured in milligrams per centimeters cubed \[mg/cm\^3\]) was measured by QCT. Percent change from Week 52 + 30 days to Week 76 + 30 days was calculated as (vBMD at Week 76 + 30 days minus vBMD at Week 52 + 30 days)/vBMD at Week 52 + 30 days x 100% and was assessed by an analysis of covariance (ANCOVA) with terms for treatment, baseline value, prior therapy, and region. Supero-anterior is the upper and front section of the FN.

Outcome measures

Outcome measures
Measure	Rosiglitazone in DB Period; Metformin in OL Period n=30 Participants Rosiglitazone (RSG) initiated at a total daily dose of 4 milligrams (mg) in the 52-week DB Period. RSG could be uptitrated to a total daily dose of 8 mg at Week 4. At Week 52, all participants were switched to open-label (OL) Metformin (MET) therapy for 24 weeks during the follow-up phase; all participants were force-titrated from 1000 mg/day to 2000 mg/day over a 4-week period. However, participants could be down-titrated to alleviate any MET-related tolerability issues.	Metformin in DB Period; Metformin in OL Period n=30 Participants Metformin (MET) initiated at a total daily dose of 1000 mg in the 52-week DB Period. MET could be uptitrated to 1500 mg/day at Week 2 and to 2000 mg/day at Week 4. At Week 52, all participants were switched to open-label MET therapy for 24 weeks during the follow-up phase; all participants were force-titrated from 1000 mg/day to 2000 mg/day over a 4-week period. However, participants could be down-titrated to alleviate any MET-related tolerability issues.
Adjusted Percent Change in Femoral Neck (FN) Supero-anterior Integral, Trabecular, and Cortical vBMD Via QCT From Week 52+30 Days to Week 76 + 30 Days Integral	2.96 percent change Standard Error 2.202	-1.81 percent change Standard Error 2.609
Adjusted Percent Change in Femoral Neck (FN) Supero-anterior Integral, Trabecular, and Cortical vBMD Via QCT From Week 52+30 Days to Week 76 + 30 Days Trabecular	-2.78 percent change Standard Error 4.677	6.63 percent change Standard Error 5.531
Adjusted Percent Change in Femoral Neck (FN) Supero-anterior Integral, Trabecular, and Cortical vBMD Via QCT From Week 52+30 Days to Week 76 + 30 Days Cortical	1.19 percent change Standard Error 0.778	-1.28 percent change Standard Error 0.912

POST_HOC outcome

Timeframe: Week 52 + 30 days and Week 76 + 30 days

Population: Safety Population, QCT subset. Only evaluable participants with a value at Week 52 performed up to 30 days after initiating OL MET or at Week 76 performed up to 30 days after stopping OL MET for the parameter of interest were analyzed.

vBMD was measured by QCT. Change from Week 52 + 30 days to Week 76 + 30 days was calculated as vBMD at Week 76 + 30 days minus vBMD at Week 52 + 30 days and was assessed by an analysis of covariance (ANCOVA) with terms for treatment, baseline value, prior therapy, and region. Supero-anterior is the upper and front section of the FN.

Outcome measures

Outcome measures
Measure	Rosiglitazone in DB Period; Metformin in OL Period n=30 Participants Rosiglitazone (RSG) initiated at a total daily dose of 4 milligrams (mg) in the 52-week DB Period. RSG could be uptitrated to a total daily dose of 8 mg at Week 4. At Week 52, all participants were switched to open-label (OL) Metformin (MET) therapy for 24 weeks during the follow-up phase; all participants were force-titrated from 1000 mg/day to 2000 mg/day over a 4-week period. However, participants could be down-titrated to alleviate any MET-related tolerability issues.	Metformin in DB Period; Metformin in OL Period n=30 Participants Metformin (MET) initiated at a total daily dose of 1000 mg in the 52-week DB Period. MET could be uptitrated to 1500 mg/day at Week 2 and to 2000 mg/day at Week 4. At Week 52, all participants were switched to open-label MET therapy for 24 weeks during the follow-up phase; all participants were force-titrated from 1000 mg/day to 2000 mg/day over a 4-week period. However, participants could be down-titrated to alleviate any MET-related tolerability issues.
Adjusted Change in Femoral Neck (FN) Supero-anterior Cortical vBMD Via QCT From Week 52+30 Days to Week 76 + 30 Days	5.19 mg/cm^3 Standard Error 3.686	-6.24 mg/cm^3 Standard Error 4.319

POST_HOC outcome

Timeframe: Baseline, Week 52 + 30 days, and Week 76 + 30 days

Population: Safety Population, QCT subset. Only evaluable participants with a value at Baseline and at Week 52 performed up to 30 days after initiating OL MET or at Week 76 performed up to 30 days after stopping OL MET for the parameter of interest were analyzed.

Cortical thickness (measured in millimeters) was measured by QCT. Percent change was calculated as (thickness at Week 52 + 30 days(or Week 76 + 30 days) minus thickness at Baseline)/thickness at Baseline x 100%.

Outcome measures

Outcome measures
Measure	Rosiglitazone in DB Period; Metformin in OL Period n=32 Participants Rosiglitazone (RSG) initiated at a total daily dose of 4 milligrams (mg) in the 52-week DB Period. RSG could be uptitrated to a total daily dose of 8 mg at Week 4. At Week 52, all participants were switched to open-label (OL) Metformin (MET) therapy for 24 weeks during the follow-up phase; all participants were force-titrated from 1000 mg/day to 2000 mg/day over a 4-week period. However, participants could be down-titrated to alleviate any MET-related tolerability issues.	Metformin in DB Period; Metformin in OL Period n=35 Participants Metformin (MET) initiated at a total daily dose of 1000 mg in the 52-week DB Period. MET could be uptitrated to 1500 mg/day at Week 2 and to 2000 mg/day at Week 4. At Week 52, all participants were switched to open-label MET therapy for 24 weeks during the follow-up phase; all participants were force-titrated from 1000 mg/day to 2000 mg/day over a 4-week period. However, participants could be down-titrated to alleviate any MET-related tolerability issues.
Adjusted Percent Change From Baseline in Femoral Neck (FN) Supero-anterior Cortical Thickness Via QCT at Week 52 + 30 Days and Week 76 + 30 Days Week 52 + 30 days, n=32, 35	-13.45 percent change Standard Error 5.002	5.05 percent change Standard Error 5.453
Adjusted Percent Change From Baseline in Femoral Neck (FN) Supero-anterior Cortical Thickness Via QCT at Week 52 + 30 Days and Week 76 + 30 Days Week 76 + 30 days, n=31, 30	-4.23 percent change Standard Error 4.491	-4.78 percent change Standard Error 5.327

POST_HOC outcome

Timeframe: Baseline and Week 76 + 30 days

Population: Safety Population, QCT subset. Only evaluable participants with a value at Baseline and at Week 76 performed up to 30 days after stopping OL MET for the parameter of interest were analyzed.

Cortical thickness was measured by QCT. Change from baseline was calculated as thickness at Week 76 + 30 days minus thickness at Baseline.

Outcome measures

Outcome measures
Measure	Rosiglitazone in DB Period; Metformin in OL Period n=31 Participants Rosiglitazone (RSG) initiated at a total daily dose of 4 milligrams (mg) in the 52-week DB Period. RSG could be uptitrated to a total daily dose of 8 mg at Week 4. At Week 52, all participants were switched to open-label (OL) Metformin (MET) therapy for 24 weeks during the follow-up phase; all participants were force-titrated from 1000 mg/day to 2000 mg/day over a 4-week period. However, participants could be down-titrated to alleviate any MET-related tolerability issues.	Metformin in DB Period; Metformin in OL Period n=30 Participants Metformin (MET) initiated at a total daily dose of 1000 mg in the 52-week DB Period. MET could be uptitrated to 1500 mg/day at Week 2 and to 2000 mg/day at Week 4. At Week 52, all participants were switched to open-label MET therapy for 24 weeks during the follow-up phase; all participants were force-titrated from 1000 mg/day to 2000 mg/day over a 4-week period. However, participants could be down-titrated to alleviate any MET-related tolerability issues.
Adjusted Change From Baseline in Femoral Neck (FN) Supero-anterior Cortical Thickness Via QCT at Week 76 + 30 Days	-0.117 millimeters Standard Error 0.0484	-0.087 millimeters Standard Error 0.0575

POST_HOC outcome

Timeframe: Week 52 + 30 days and Week 76 + 30 days

Population: Safety Population, QCT subset. Only evaluable participants with a value at Week 52 performed up to 30 days after initiating OL MET or at Week 76 performed up to 30 days after stopping OL MET for the parameter of interest were analyzed.

Cortical thickness (measured in millimeters) was measured by QCT. Percent change was calculated as (thickness at Week 76 + 30 days minus thickness at Week 52 + 30 days)/thickness at Week 52 + 30 days x 100%.

Outcome measures

Outcome measures
Measure	Rosiglitazone in DB Period; Metformin in OL Period n=30 Participants Rosiglitazone (RSG) initiated at a total daily dose of 4 milligrams (mg) in the 52-week DB Period. RSG could be uptitrated to a total daily dose of 8 mg at Week 4. At Week 52, all participants were switched to open-label (OL) Metformin (MET) therapy for 24 weeks during the follow-up phase; all participants were force-titrated from 1000 mg/day to 2000 mg/day over a 4-week period. However, participants could be down-titrated to alleviate any MET-related tolerability issues.	Metformin in DB Period; Metformin in OL Period n=30 Participants Metformin (MET) initiated at a total daily dose of 1000 mg in the 52-week DB Period. MET could be uptitrated to 1500 mg/day at Week 2 and to 2000 mg/day at Week 4. At Week 52, all participants were switched to open-label MET therapy for 24 weeks during the follow-up phase; all participants were force-titrated from 1000 mg/day to 2000 mg/day over a 4-week period. However, participants could be down-titrated to alleviate any MET-related tolerability issues.
Adjusted Percent Change in Femoral Neck (FN) Supero-anterior Cortical Thickness Via QCT From Week 52 + 30 Days to Week 76 + 30 Days	14.02 percent change Standard Error 6.779	-13.65 percent change Standard Error 7.995

POST_HOC outcome

Timeframe: Week 52 + 30 days and Week 76 + 30 days

Population: Safety Population, QCT subset. Only evaluable participants with a value at Week 52 performed up to 30 days after initiating OL MET or at Week 76 performed up to 30 days after stopping OL MET for the parameter of interest were analyzed.

Cortical thickness was measured by QCT. Change was calculated as thickness at Week 76 + 30 days minus thickness at Week 52 + 30 days.

Outcome measures

Outcome measures
Measure	Rosiglitazone in DB Period; Metformin in OL Period n=30 Participants Rosiglitazone (RSG) initiated at a total daily dose of 4 milligrams (mg) in the 52-week DB Period. RSG could be uptitrated to a total daily dose of 8 mg at Week 4. At Week 52, all participants were switched to open-label (OL) Metformin (MET) therapy for 24 weeks during the follow-up phase; all participants were force-titrated from 1000 mg/day to 2000 mg/day over a 4-week period. However, participants could be down-titrated to alleviate any MET-related tolerability issues.	Metformin in DB Period; Metformin in OL Period n=30 Participants Metformin (MET) initiated at a total daily dose of 1000 mg in the 52-week DB Period. MET could be uptitrated to 1500 mg/day at Week 2 and to 2000 mg/day at Week 4. At Week 52, all participants were switched to open-label MET therapy for 24 weeks during the follow-up phase; all participants were force-titrated from 1000 mg/day to 2000 mg/day over a 4-week period. However, participants could be down-titrated to alleviate any MET-related tolerability issues.
Adjusted Change in Femoral Neck (FN) Supero-anterior Cortical Thickness Via QCT From Week 52+30 Days to Week 76 + 30 Days	0.11 millimeters Standard Error 0.052	-0.13 millimeters Standard Error 0.061

POST_HOC outcome

Timeframe: Baseline, Week 52 + 30 days, and Week 76 + 30 days

Population: Safety Population, QCT subset. Only evaluable participants with a value at Baseline and at Week 52 performed up to 30 days after initiating OL MET or at Week 76 performed up to 30 days after stopping OL MET for the parameter of interest were analyzed.

vBMD (measured in milligrams per centimeters cubed \[mg/cm\^3\]) was measured by QCT. Percent change from Baseline at Week 52 + 30 days or Week 76 + 30 days was calculated as (vBMD at Week 52 + 30 days (or Week 76 + 30 days) minus vBMD at baseline)/vBMD at Baseline x 100% and was assessed by an analysis of covariance (ANCOVA) with terms for treatment, baseline value, prior therapy, and region. Infero-posterior is the lower and back section of the FN.

Outcome measures

Outcome measures
Measure	Rosiglitazone in DB Period; Metformin in OL Period n=32 Participants Rosiglitazone (RSG) initiated at a total daily dose of 4 milligrams (mg) in the 52-week DB Period. RSG could be uptitrated to a total daily dose of 8 mg at Week 4. At Week 52, all participants were switched to open-label (OL) Metformin (MET) therapy for 24 weeks during the follow-up phase; all participants were force-titrated from 1000 mg/day to 2000 mg/day over a 4-week period. However, participants could be down-titrated to alleviate any MET-related tolerability issues.	Metformin in DB Period; Metformin in OL Period n=35 Participants Metformin (MET) initiated at a total daily dose of 1000 mg in the 52-week DB Period. MET could be uptitrated to 1500 mg/day at Week 2 and to 2000 mg/day at Week 4. At Week 52, all participants were switched to open-label MET therapy for 24 weeks during the follow-up phase; all participants were force-titrated from 1000 mg/day to 2000 mg/day over a 4-week period. However, participants could be down-titrated to alleviate any MET-related tolerability issues.
Adjusted Percent Change From Baseline in Femoral Neck (FN) Infero-posterior Integral, Trabecular, and Cortical vBMD Via QCT at Week 52 + 30 Days and Week 76 + 30 Days Week 52 + 30 days, Integral, n=32, 35	-4.11 percent change Standard Error 1.074	1.74 percent change Standard Error 1.200
Adjusted Percent Change From Baseline in Femoral Neck (FN) Infero-posterior Integral, Trabecular, and Cortical vBMD Via QCT at Week 52 + 30 Days and Week 76 + 30 Days Week 52 + 30 days, Trabecular, n=32, 35	-84.08 percent change Standard Error 270.700	282.16 percent change Standard Error 297.445
Adjusted Percent Change From Baseline in Femoral Neck (FN) Infero-posterior Integral, Trabecular, and Cortical vBMD Via QCT at Week 52 + 30 Days and Week 76 + 30 Days Week 52 + 30 days, Cortical, n=32, 35	-3.42 percent change Standard Error 1.531	1.14 percent change Standard Error 1.694
Adjusted Percent Change From Baseline in Femoral Neck (FN) Infero-posterior Integral, Trabecular, and Cortical vBMD Via QCT at Week 52 + 30 Days and Week 76 + 30 Days Week 76 + 30 days, Integral, n=31, 30	-3.11 percent change Standard Error 0.933	0.01 percent change Standard Error 1.147
Adjusted Percent Change From Baseline in Femoral Neck (FN) Infero-posterior Integral, Trabecular, and Cortical vBMD Via QCT at Week 52 + 30 Days and Week 76 + 30 Days Week 76 + 30 days, Trabecular, n=31, 30	24.46 percent change Standard Error 17.473	13.54 percent change Standard Error 20.790
Adjusted Percent Change From Baseline in Femoral Neck (FN) Infero-posterior Integral, Trabecular, and Cortical vBMD Via QCT at Week 52 + 30 Days and Week 76 + 30 Days Week 76 + 30 days, Cortical, n=31, 30	-1.32 percent change Standard Error 1.234	-1.17 percent change Standard Error 1.492

POST_HOC outcome

Timeframe: Baseline and Week 76 + 30 days

Population: Safety Population, QCT subset. Only evaluable participants with a value at Baseline and at Week 76 performed up to 30 days after stopping OL MET for the parameter of interest were analyzed.

vBMD was measured by QCT. Change from Baseline at Week 76 + 30 days was calculated as vBMD at Week 76 + 30 days minus vBMD at baseline and was assessed by an analysis of covariance (ANCOVA) with terms for treatment, baseline value, prior therapy, and region. Infero-posterior is the lower and back section of the FN.

Outcome measures

Outcome measures
Measure	Rosiglitazone in DB Period; Metformin in OL Period n=31 Participants Rosiglitazone (RSG) initiated at a total daily dose of 4 milligrams (mg) in the 52-week DB Period. RSG could be uptitrated to a total daily dose of 8 mg at Week 4. At Week 52, all participants were switched to open-label (OL) Metformin (MET) therapy for 24 weeks during the follow-up phase; all participants were force-titrated from 1000 mg/day to 2000 mg/day over a 4-week period. However, participants could be down-titrated to alleviate any MET-related tolerability issues.	Metformin in DB Period; Metformin in OL Period n=30 Participants Metformin (MET) initiated at a total daily dose of 1000 mg in the 52-week DB Period. MET could be uptitrated to 1500 mg/day at Week 2 and to 2000 mg/day at Week 4. At Week 52, all participants were switched to open-label MET therapy for 24 weeks during the follow-up phase; all participants were force-titrated from 1000 mg/day to 2000 mg/day over a 4-week period. However, participants could be down-titrated to alleviate any MET-related tolerability issues.
Adjusted Change From Baseline in Femoral Neck (FN) Infero-posterior Cortical vBMD Via QCT at Week 76 + 30 Days	-12.424 mg/cm^3 Standard Error 8.9945	-10.244 mg/cm^3 Standard Error 10.8703

POST_HOC outcome

Timeframe: Week 52 + 30 days and Week 76 + 30 days

Population: Safety Population, QCT subset. Only evaluable participants with a value at Week 52 performed up to 30 days after initiating OL MET or at Week 76 performed up to 30 days after stopping OL MET for the parameter of interest were analyzed.

vBMD (measured in milligrams per centimeters cubed \[mg/cm\^3\]) was measured by QCT. Percent change from Week 52 + 30 days to Week 76 + 30 days was calculated as (vBMD at Week 76 + 30 days minus vBMD at Week 52 + 30 days)/vBMD at Week 52 + 30 days x 100% and was assessed by an analysis of covariance (ANCOVA) with terms for treatment, baseline value, prior therapy, and region. Infero-posterior is the lower and back section of the FN.

Outcome measures

Outcome measures
Measure	Rosiglitazone in DB Period; Metformin in OL Period n=30 Participants Rosiglitazone (RSG) initiated at a total daily dose of 4 milligrams (mg) in the 52-week DB Period. RSG could be uptitrated to a total daily dose of 8 mg at Week 4. At Week 52, all participants were switched to open-label (OL) Metformin (MET) therapy for 24 weeks during the follow-up phase; all participants were force-titrated from 1000 mg/day to 2000 mg/day over a 4-week period. However, participants could be down-titrated to alleviate any MET-related tolerability issues.	Metformin in DB Period; Metformin in OL Period n=30 Participants Metformin (MET) initiated at a total daily dose of 1000 mg in the 52-week DB Period. MET could be uptitrated to 1500 mg/day at Week 2 and to 2000 mg/day at Week 4. At Week 52, all participants were switched to open-label MET therapy for 24 weeks during the follow-up phase; all participants were force-titrated from 1000 mg/day to 2000 mg/day over a 4-week period. However, participants could be down-titrated to alleviate any MET-related tolerability issues.
Adjusted Percent Change in Femoral Neck (FN) Infero-posterior Integral, Trabecular, and Cortical vBMD Via QCT From Week 52+30 Days to Week 76 + 30 Days Integral	1.47 percent change Standard Error 1.183	-1.87 percent change Standard Error 1.435
Adjusted Percent Change in Femoral Neck (FN) Infero-posterior Integral, Trabecular, and Cortical vBMD Via QCT From Week 52+30 Days to Week 76 + 30 Days Trabecular	-39.81 percent change Standard Error 130.071	161.81 percent change Standard Error 154.179
Adjusted Percent Change in Femoral Neck (FN) Infero-posterior Integral, Trabecular, and Cortical vBMD Via QCT From Week 52+30 Days to Week 76 + 30 Days Cortical	2.67 percent change Standard Error 1.728	-2.50 percent change Standard Error 2.076

POST_HOC outcome

Timeframe: Week 52 + 30 days and Week 76 + 30 days

Population: Safety Population, QCT subset. Only evaluable participants with a value at Week 52 performed up to 30 days after initiating OL MET or at Week 76 performed up to 30 days after stopping OL MET for the parameter of interest were analyzed.

vBMD was measured by QCT. Change from Week 52 + 30 days to Week 76 + 30 days was calculated as vBMD at Week 76 + 30 days minus vBMD at Week 52 + 30 days and was assessed by an analysis of covariance (ANCOVA) with terms for treatment, baseline value, prior therapy, and region. Infero-posterior is the lower and back section of the FN.

Outcome measures

Outcome measures
Measure	Rosiglitazone in DB Period; Metformin in OL Period n=30 Participants Rosiglitazone (RSG) initiated at a total daily dose of 4 milligrams (mg) in the 52-week DB Period. RSG could be uptitrated to a total daily dose of 8 mg at Week 4. At Week 52, all participants were switched to open-label (OL) Metformin (MET) therapy for 24 weeks during the follow-up phase; all participants were force-titrated from 1000 mg/day to 2000 mg/day over a 4-week period. However, participants could be down-titrated to alleviate any MET-related tolerability issues.	Metformin in DB Period; Metformin in OL Period n=30 Participants Metformin (MET) initiated at a total daily dose of 1000 mg in the 52-week DB Period. MET could be uptitrated to 1500 mg/day at Week 2 and to 2000 mg/day at Week 4. At Week 52, all participants were switched to open-label MET therapy for 24 weeks during the follow-up phase; all participants were force-titrated from 1000 mg/day to 2000 mg/day over a 4-week period. However, participants could be down-titrated to alleviate any MET-related tolerability issues.
Adjusted Change in Femoral Neck (FN) Infero-posterior Cortical vBMD Via QCT From Week 52 + 30 Days to Week 76 + 30 Days	15.48 mg/cm^3 Standard Error 11.544	-17.59 mg/cm^3 Standard Error 13.865

POST_HOC outcome

Timeframe: Baseline, Week 52 + 30 days, and Week 76 + 30 days

Population: Safety Population, QCT subset. Only evaluable participants with a value at Baseline and at Week 52 performed up to 30 days after initiating OL MET or Week 76 performed up to 30 days after stopping OL MET for the parameter of interest were analyzed.

Cortical thickness (measured in millimeters) was measured by QCT. Percent change was calculated as (thickness at Week 52 + 30 days (or Week 76 + 30 days) minus thickness at Baseline)/thickness at Baseline x 100%.

Outcome measures

Outcome measures
Measure	Rosiglitazone in DB Period; Metformin in OL Period n=32 Participants Rosiglitazone (RSG) initiated at a total daily dose of 4 milligrams (mg) in the 52-week DB Period. RSG could be uptitrated to a total daily dose of 8 mg at Week 4. At Week 52, all participants were switched to open-label (OL) Metformin (MET) therapy for 24 weeks during the follow-up phase; all participants were force-titrated from 1000 mg/day to 2000 mg/day over a 4-week period. However, participants could be down-titrated to alleviate any MET-related tolerability issues.	Metformin in DB Period; Metformin in OL Period n=35 Participants Metformin (MET) initiated at a total daily dose of 1000 mg in the 52-week DB Period. MET could be uptitrated to 1500 mg/day at Week 2 and to 2000 mg/day at Week 4. At Week 52, all participants were switched to open-label MET therapy for 24 weeks during the follow-up phase; all participants were force-titrated from 1000 mg/day to 2000 mg/day over a 4-week period. However, participants could be down-titrated to alleviate any MET-related tolerability issues.
Adjusted Percent Change From Baseline in Femoral Neck (FN) Infero-posterior Cortical Thickness Via QCT at Week 52 + 30 Days and Week 76 + 30 Days Week 52 + 30 days, n=32, 35	0.47 percent change Standard Error 1.977	-1.27 percent change Standard Error 2.180
Adjusted Percent Change From Baseline in Femoral Neck (FN) Infero-posterior Cortical Thickness Via QCT at Week 52 + 30 Days and Week 76 + 30 Days Week 76 + 30 days, n=31, 30	-1.46 percent change Standard Error 1.593	-0.11 percent change Standard Error 1.910

POST_HOC outcome

Timeframe: Baseline and Week 76 + 30 days

Population: Safety Population, QCT subset. Only evaluable participants with a value at Baseline and at Week 76 performed up to 30 days after stopping OL MET for the parameter of interest were analyzed.

Cortical thickness was measured by QCT. Change from Baseline was calculated as thickness at Week 76 + 30 days minus thickness at Baseline.

Outcome measures

Outcome measures
Measure	Rosiglitazone in DB Period; Metformin in OL Period n=31 Participants Rosiglitazone (RSG) initiated at a total daily dose of 4 milligrams (mg) in the 52-week DB Period. RSG could be uptitrated to a total daily dose of 8 mg at Week 4. At Week 52, all participants were switched to open-label (OL) Metformin (MET) therapy for 24 weeks during the follow-up phase; all participants were force-titrated from 1000 mg/day to 2000 mg/day over a 4-week period. However, participants could be down-titrated to alleviate any MET-related tolerability issues.	Metformin in DB Period; Metformin in OL Period n=30 Participants Metformin (MET) initiated at a total daily dose of 1000 mg in the 52-week DB Period. MET could be uptitrated to 1500 mg/day at Week 2 and to 2000 mg/day at Week 4. At Week 52, all participants were switched to open-label MET therapy for 24 weeks during the follow-up phase; all participants were force-titrated from 1000 mg/day to 2000 mg/day over a 4-week period. However, participants could be down-titrated to alleviate any MET-related tolerability issues.
Adjusted Change From Baseline in Femoral Neck (FN) Infero-posterior Cortical Thickness Via QCT at Week 76 + 30 Days	-0.082 millimeters Standard Error 0.0816	-0.048 millimeters Standard Error 0.0978

POST_HOC outcome

Timeframe: Week 52 + 30 days and Week 76 + 30 days

Population: Safety Population, QCT subset. Only evaluable participants with a value at Week 52 performed up to 30 days after initiating OL MET or at Week 76 performed up to 30 days after stopping OL MET for the parameter of interest were analyzed.

Cortical thickness (measured in millimeters) was measured by QCT. Percent change was calculated as (thickness at Week 76 + 30 days minus thickness at Week 52 + 30 days)/thickness at Week 52 + 30 days x 100%.

Outcome measures

Outcome measures
Measure	Rosiglitazone in DB Period; Metformin in OL Period n=30 Participants Rosiglitazone (RSG) initiated at a total daily dose of 4 milligrams (mg) in the 52-week DB Period. RSG could be uptitrated to a total daily dose of 8 mg at Week 4. At Week 52, all participants were switched to open-label (OL) Metformin (MET) therapy for 24 weeks during the follow-up phase; all participants were force-titrated from 1000 mg/day to 2000 mg/day over a 4-week period. However, participants could be down-titrated to alleviate any MET-related tolerability issues.	Metformin in DB Period; Metformin in OL Period n=30 Participants Metformin (MET) initiated at a total daily dose of 1000 mg in the 52-week DB Period. MET could be uptitrated to 1500 mg/day at Week 2 and to 2000 mg/day at Week 4. At Week 52, all participants were switched to open-label MET therapy for 24 weeks during the follow-up phase; all participants were force-titrated from 1000 mg/day to 2000 mg/day over a 4-week period. However, participants could be down-titrated to alleviate any MET-related tolerability issues.
Adjusted Percent Change in Femoral Neck (FN) Infero-posterior Cortical Thickness Via QCT From Week 52 + 30 Days to Week 76 + 30 Days	-1.48 percent change Standard Error 1.552	2.04 percent change Standard Error 1.846

POST_HOC outcome

Timeframe: Week 52 + 30 days and Week 76 + 30 days

Population: Safety Population, QCT subset. Only evaluable participants with a value at Week 52 performed up to 30 days after initiating OL MET or at Week 76 performed up to 30 days after stopping OL MET for the parameter of interest were analyzed.

Cortical thickness was measured by QCT. Change was calculated as thickness at Week 76 + 30 days minus thickness at Week 52 + 30 days.

Outcome measures

Outcome measures
Measure	Rosiglitazone in DB Period; Metformin in OL Period n=30 Participants Rosiglitazone (RSG) initiated at a total daily dose of 4 milligrams (mg) in the 52-week DB Period. RSG could be uptitrated to a total daily dose of 8 mg at Week 4. At Week 52, all participants were switched to open-label (OL) Metformin (MET) therapy for 24 weeks during the follow-up phase; all participants were force-titrated from 1000 mg/day to 2000 mg/day over a 4-week period. However, participants could be down-titrated to alleviate any MET-related tolerability issues.	Metformin in DB Period; Metformin in OL Period n=30 Participants Metformin (MET) initiated at a total daily dose of 1000 mg in the 52-week DB Period. MET could be uptitrated to 1500 mg/day at Week 2 and to 2000 mg/day at Week 4. At Week 52, all participants were switched to open-label MET therapy for 24 weeks during the follow-up phase; all participants were force-titrated from 1000 mg/day to 2000 mg/day over a 4-week period. However, participants could be down-titrated to alleviate any MET-related tolerability issues.
Adjusted Change in Femoral Neck (FN) Infero-posterior Cortical Thickness Via QCT From Week 52 + 30 Days to Week 76 + 30 Days	-0.08 millimeters Standard Error 0.078	0.07 millimeters Standard Error 0.093

POST_HOC outcome

Timeframe: Baseline, Week 52 + 30 days, and Week 76 + 30 days

Population: Safety Population, QCT subset. Only evaluable participants with a value at Baseline and at Week 52 performed up to 30 days after initiating OL MET or at Week 76 performed up to 30 days after stopping OL MET for the parameter of interest were analyzed.

vBMD (measured in milligrams per centimeters cubed \[mg/cm\^3\]) was measured by QCT. Percent change from Baseline at Week 52 + 30 days or Week 76 + 30 days was calculated as (vBMD at Week 52 + 30 days (orWeek 76 + 30 days) minus vBMD at baseline)/vBMD at Baseline x 100% and was assessed by an analysis of covariance (ANCOVA) with terms for treatment, baseline value, prior therapy, and region. Infero-anterior is the lower and front section of the FN.

Outcome measures

Outcome measures
Measure	Rosiglitazone in DB Period; Metformin in OL Period n=32 Participants Rosiglitazone (RSG) initiated at a total daily dose of 4 milligrams (mg) in the 52-week DB Period. RSG could be uptitrated to a total daily dose of 8 mg at Week 4. At Week 52, all participants were switched to open-label (OL) Metformin (MET) therapy for 24 weeks during the follow-up phase; all participants were force-titrated from 1000 mg/day to 2000 mg/day over a 4-week period. However, participants could be down-titrated to alleviate any MET-related tolerability issues.	Metformin in DB Period; Metformin in OL Period n=35 Participants Metformin (MET) initiated at a total daily dose of 1000 mg in the 52-week DB Period. MET could be uptitrated to 1500 mg/day at Week 2 and to 2000 mg/day at Week 4. At Week 52, all participants were switched to open-label MET therapy for 24 weeks during the follow-up phase; all participants were force-titrated from 1000 mg/day to 2000 mg/day over a 4-week period. However, participants could be down-titrated to alleviate any MET-related tolerability issues.
Adjusted Percent Change From Baseline in Femoral Neck (FN) Infero-anterior Integral, Trabecular, and Cortical vBMD Via QCT at Week 52 + 30 Days and Week 76 + 30 Days Week 52 + 30 days, Integral, n=32, 35	-4.35 percent change Standard Error 1.950	1.26 percent change Standard Error 2.163
Adjusted Percent Change From Baseline in Femoral Neck (FN) Infero-anterior Integral, Trabecular, and Cortical vBMD Via QCT at Week 52 + 30 Days and Week 76 + 30 Days Week 52, Trabecular, n=32, 35	-161.59 percent change Standard Error 774.589	930.71 percent change Standard Error 851.727
Adjusted Percent Change From Baseline in Femoral Neck (FN) Infero-anterior Integral, Trabecular, and Cortical vBMD Via QCT at Week 52 + 30 Days and Week 76 + 30 Days Week 52, Cortical, n=32, 35	-1.85 percent change Standard Error 1.309	0.85 percent change Standard Error 1.563
Adjusted Percent Change From Baseline in Femoral Neck (FN) Infero-anterior Integral, Trabecular, and Cortical vBMD Via QCT at Week 52 + 30 Days and Week 76 + 30 Days Week 76 + 30 days, Integral, n=31, 30	-0.29 percent change Standard Error 2.301	0.54 percent change Standard Error 2.810
Adjusted Percent Change From Baseline in Femoral Neck (FN) Infero-anterior Integral, Trabecular, and Cortical vBMD Via QCT at Week 52 + 30 Days and Week 76 + 30 Days Week 76 + 30 days, Trabecular, n=31, 30	81.29 percent change Standard Error 35.959	37.81 percent change Standard Error 42.791
Adjusted Percent Change From Baseline in Femoral Neck (FN) Infero-anterior Integral, Trabecular, and Cortical vBMD Via QCT at Week 52 + 30 Days and Week 76 + 30 Days Week 76 + 30 days, Cortical, n=31, 30	1.45 percent change Standard Error 1.149	-0.63 percent change Standard Error 1.409

POST_HOC outcome

Timeframe: Baseline and Week 76 + 30 days

Population: Safety Population, QCT subset. Only evaluable participants with a value at Baseline and at Week 76 performed up to 30 days after stopping OL MET for the parameter of interest were analyzed.

vBMD was measured by QCT. Change from Baseline at Week 76 + 30 days was calculated as vBMD at Week 76 + 30 days minus vBMD at baseline and was assessed by an analysis of covariance (ANCOVA) with terms for treatment, baseline value, prior therapy, and region. Infero-anterior is the lower and front section of the FN.

Outcome measures

Outcome measures
Measure	Rosiglitazone in DB Period; Metformin in OL Period n=31 Participants Rosiglitazone (RSG) initiated at a total daily dose of 4 milligrams (mg) in the 52-week DB Period. RSG could be uptitrated to a total daily dose of 8 mg at Week 4. At Week 52, all participants were switched to open-label (OL) Metformin (MET) therapy for 24 weeks during the follow-up phase; all participants were force-titrated from 1000 mg/day to 2000 mg/day over a 4-week period. However, participants could be down-titrated to alleviate any MET-related tolerability issues.	Metformin in DB Period; Metformin in OL Period n=30 Participants Metformin (MET) initiated at a total daily dose of 1000 mg in the 52-week DB Period. MET could be uptitrated to 1500 mg/day at Week 2 and to 2000 mg/day at Week 4. At Week 52, all participants were switched to open-label MET therapy for 24 weeks during the follow-up phase; all participants were force-titrated from 1000 mg/day to 2000 mg/day over a 4-week period. However, participants could be down-titrated to alleviate any MET-related tolerability issues.
Adjusted Change From Baseline in Femoral Neck (FN) Infero-anterior Cortical vBMD Via QCT at Week 76 + 30 Days	7.901 mg/cm^3 Standard Error 6.9912	-5.025 mg/cm^3 Standard Error 8.5722

POST_HOC outcome

Timeframe: Week 52 + 30 days and Week 76 + 30 days

Population: Safety Population, QCT subset. Only evaluable participants with a value at Week 52 performed up to 30 days after initiating OL MET or at Week 76 performed up to 30 days after stopping OL MET for the parameter of interest were analyzed.

vBMD (measured in milligrams per centimeters cubed \[mg/cm\^3\]) was measured by QCT. Percent change from Week 52 + 30 days to Week 76 + 30 days was calculated as (vBMD at Week 76 + 30 days minus vBMD at Week 52 + 30 days)/vBMD at Week 52 + 30 days x 100% and was assessed by an analysis of covariance (ANCOVA) with terms for treatment, baseline value, prior therapy, and region. Infero-anterior is the lower and front section of the FN.

Outcome measures

Outcome measures
Measure	Rosiglitazone in DB Period; Metformin in OL Period n=30 Participants Rosiglitazone (RSG) initiated at a total daily dose of 4 milligrams (mg) in the 52-week DB Period. RSG could be uptitrated to a total daily dose of 8 mg at Week 4. At Week 52, all participants were switched to open-label (OL) Metformin (MET) therapy for 24 weeks during the follow-up phase; all participants were force-titrated from 1000 mg/day to 2000 mg/day over a 4-week period. However, participants could be down-titrated to alleviate any MET-related tolerability issues.	Metformin in DB Period; Metformin in OL Period n=30 Participants Metformin (MET) initiated at a total daily dose of 1000 mg in the 52-week DB Period. MET could be uptitrated to 1500 mg/day at Week 2 and to 2000 mg/day at Week 4. At Week 52, all participants were switched to open-label MET therapy for 24 weeks during the follow-up phase; all participants were force-titrated from 1000 mg/day to 2000 mg/day over a 4-week period. However, participants could be down-titrated to alleviate any MET-related tolerability issues.
Adjusted Percent Change in Femoral Neck (FN) Infero-anterior Integral, Trabecular, and Cortical vBMD Via QCT From Week 52+30 Days to Week 76 + 30 Days Integral	5.05 percent change Standard Error 1.878	0.38 percent change Standard Error 2.268
Adjusted Percent Change in Femoral Neck (FN) Infero-anterior Integral, Trabecular, and Cortical vBMD Via QCT From Week 52+30 Days to Week 76 + 30 Days Trabecular	-90.60 percent change Standard Error 167.792	260.13 percent change Standard Error 199.323
Adjusted Percent Change in Femoral Neck (FN) Infero-anterior Integral, Trabecular, and Cortical vBMD Via QCT From Week 52+30 Days to Week 76 + 30 Days Cortical	3.68 percent change Standard Error 1.649	-1.64 percent change Standard Error 2.016

POST_HOC outcome

Timeframe: Week 52 + 30 days and Week 76 + 30 days

Population: Safety Population, QCT subset. Only evaluable participants with a value at Week 52 performed up to 30 days after initiating OL MET or at Week 76 performed up to 30 days after stopping OL MET for the parameter of interest were analyzed.

vBMD was measured by QCT. Change from Week 52 + 30 days to Week 76 + 30 days was calculated as vBMD at Week 76 + 30 days minus vBMD at Week 52 + 30 days and was assessed by an analysis of covariance (ANCOVA) with terms for treatment, baseline value, prior therapy, and region. Infero-anterior is the lower and front section of the FN.

Outcome measures

Outcome measures
Measure	Rosiglitazone in DB Period; Metformin in OL Period n=30 Participants Rosiglitazone (RSG) initiated at a total daily dose of 4 milligrams (mg) in the 52-week DB Period. RSG could be uptitrated to a total daily dose of 8 mg at Week 4. At Week 52, all participants were switched to open-label (OL) Metformin (MET) therapy for 24 weeks during the follow-up phase; all participants were force-titrated from 1000 mg/day to 2000 mg/day over a 4-week period. However, participants could be down-titrated to alleviate any MET-related tolerability issues.	Metformin in DB Period; Metformin in OL Period n=30 Participants Metformin (MET) initiated at a total daily dose of 1000 mg in the 52-week DB Period. MET could be uptitrated to 1500 mg/day at Week 2 and to 2000 mg/day at Week 4. At Week 52, all participants were switched to open-label MET therapy for 24 weeks during the follow-up phase; all participants were force-titrated from 1000 mg/day to 2000 mg/day over a 4-week period. However, participants could be down-titrated to alleviate any MET-related tolerability issues.
Adjusted Change in Femoral Neck (FN) Infero-anterior Cortical vBMD Via QCT From Week 52 + 30 Days to Week 76 + 30 Days	20.15 mg/cm^3 Standard Error 9.677	-10.73 mg/cm^3 Standard Error 11.830

POST_HOC outcome

Timeframe: Baseline, Week 52 + 30 days, and Week 76 + 30 days

Population: Safety Population, QCT subset. Only evaluable participants with a value at Baseline and at Week 52 performed up to 30 days after initiating OL MET or at Week 76 performed up to 30 days after stopping OL MET for the parameter of interest were analyzed.

Cortical thickness (measured in millimeters) was measured by QCT. Percent change was calculated as (thickness at Week 52 + 30 days (orWeek 76 + 30 days) minus thickness at Baseline)/thickness at Baseline x 100%.

Outcome measures

Outcome measures
Measure	Rosiglitazone in DB Period; Metformin in OL Period n=32 Participants Rosiglitazone (RSG) initiated at a total daily dose of 4 milligrams (mg) in the 52-week DB Period. RSG could be uptitrated to a total daily dose of 8 mg at Week 4. At Week 52, all participants were switched to open-label (OL) Metformin (MET) therapy for 24 weeks during the follow-up phase; all participants were force-titrated from 1000 mg/day to 2000 mg/day over a 4-week period. However, participants could be down-titrated to alleviate any MET-related tolerability issues.	Metformin in DB Period; Metformin in OL Period n=35 Participants Metformin (MET) initiated at a total daily dose of 1000 mg in the 52-week DB Period. MET could be uptitrated to 1500 mg/day at Week 2 and to 2000 mg/day at Week 4. At Week 52, all participants were switched to open-label MET therapy for 24 weeks during the follow-up phase; all participants were force-titrated from 1000 mg/day to 2000 mg/day over a 4-week period. However, participants could be down-titrated to alleviate any MET-related tolerability issues.
Adjusted Percent Change From Baseline in Femoral Neck (FN) Infero-anterior Cortical Thickness Via QCT at Week 52 + 30 Days and Week 76 + 30 Days Week 52 + 30 days, n=32, 35	-6.05 percent change Standard Error 2.393	0.64 percent change Standard Error 2.656
Adjusted Percent Change From Baseline in Femoral Neck (FN) Infero-anterior Cortical Thickness Via QCT at Week 52 + 30 Days and Week 76 + 30 Days Week 76 + 30 days, n=31, 30	-3.59 percent change Standard Error 2.804	0.39 percent change Standard Error 3.421

POST_HOC outcome

Timeframe: Baseline and Week 76 + 30 days

Population: Safety Population, QCT subset. Only evaluable participants with a value at Baseline and at Week 76 performed up to 30 days after stopping OL MET for the parameter of interest were analyzed.

Cortical thickness was measured by QCT. Change was calculated as thickness at Week 76 + 30 days minus thickness at Baseline.

Outcome measures

Outcome measures
Measure	Rosiglitazone in DB Period; Metformin in OL Period n=31 Participants Rosiglitazone (RSG) initiated at a total daily dose of 4 milligrams (mg) in the 52-week DB Period. RSG could be uptitrated to a total daily dose of 8 mg at Week 4. At Week 52, all participants were switched to open-label (OL) Metformin (MET) therapy for 24 weeks during the follow-up phase; all participants were force-titrated from 1000 mg/day to 2000 mg/day over a 4-week period. However, participants could be down-titrated to alleviate any MET-related tolerability issues.	Metformin in DB Period; Metformin in OL Period n=30 Participants Metformin (MET) initiated at a total daily dose of 1000 mg in the 52-week DB Period. MET could be uptitrated to 1500 mg/day at Week 2 and to 2000 mg/day at Week 4. At Week 52, all participants were switched to open-label MET therapy for 24 weeks during the follow-up phase; all participants were force-titrated from 1000 mg/day to 2000 mg/day over a 4-week period. However, participants could be down-titrated to alleviate any MET-related tolerability issues.
Adjusted Change From Baseline in Femoral Neck (FN) Infero-anterior Cortical Thickness Via QCT at Week 76 + 30 Days	-0.120 millimeters Standard Error 0.0931	-0.040 millimeters Standard Error 0.1135

POST_HOC outcome

Timeframe: Week 52 + 30 days and Week 76 + 30 days

Population: Safety Population, QCT subset. Only evaluable participants with a value at Week 52 performed up to 30 days after initiating OL MET or at Week 76 performed up to 30 days after stopping OL MET for the parameter of interest were analyzed.

Cortical thickness (measured in millimeters) was measured by QCT. Percent change was calculated as (thickness at Week 76 + 30 days minus thickness at Week 52 + 30 days)/thickness at Week 52 + 30 days x 100%.

Outcome measures

Outcome measures
Measure	Rosiglitazone in DB Period; Metformin in OL Period n=30 Participants Rosiglitazone (RSG) initiated at a total daily dose of 4 milligrams (mg) in the 52-week DB Period. RSG could be uptitrated to a total daily dose of 8 mg at Week 4. At Week 52, all participants were switched to open-label (OL) Metformin (MET) therapy for 24 weeks during the follow-up phase; all participants were force-titrated from 1000 mg/day to 2000 mg/day over a 4-week period. However, participants could be down-titrated to alleviate any MET-related tolerability issues.	Metformin in DB Period; Metformin in OL Period n=30 Participants Metformin (MET) initiated at a total daily dose of 1000 mg in the 52-week DB Period. MET could be uptitrated to 1500 mg/day at Week 2 and to 2000 mg/day at Week 4. At Week 52, all participants were switched to open-label MET therapy for 24 weeks during the follow-up phase; all participants were force-titrated from 1000 mg/day to 2000 mg/day over a 4-week period. However, participants could be down-titrated to alleviate any MET-related tolerability issues.
Adjusted Percent Change in Femoral Neck (FN) Infero-anterior Cortical Thickness Via QCT From Week 52 + 30 Days to Week 76 + 30 Days	3.12 percent change Standard Error 2.127	1.56 percent change Standard Error 2.257

POST_HOC outcome

Timeframe: Week 52 + 30 days and Week 76 + 30 days

Population: Safety Population, QCT subset. Only evaluable participants with a value at Week 52 performed up to 30 days after initiating OL MET or at Week 76 performed up to 30 days after stopping OL MET for the parameter of interest were analyzed.

Cortical thickness was measured by QCT. Change was calculated as thickness at Week 76 + 30 days minus thickness at Week 52 + 30 days.

Outcome measures

Outcome measures
Measure	Rosiglitazone in DB Period; Metformin in OL Period n=30 Participants Rosiglitazone (RSG) initiated at a total daily dose of 4 milligrams (mg) in the 52-week DB Period. RSG could be uptitrated to a total daily dose of 8 mg at Week 4. At Week 52, all participants were switched to open-label (OL) Metformin (MET) therapy for 24 weeks during the follow-up phase; all participants were force-titrated from 1000 mg/day to 2000 mg/day over a 4-week period. However, participants could be down-titrated to alleviate any MET-related tolerability issues.	Metformin in DB Period; Metformin in OL Period n=30 Participants Metformin (MET) initiated at a total daily dose of 1000 mg in the 52-week DB Period. MET could be uptitrated to 1500 mg/day at Week 2 and to 2000 mg/day at Week 4. At Week 52, all participants were switched to open-label MET therapy for 24 weeks during the follow-up phase; all participants were force-titrated from 1000 mg/day to 2000 mg/day over a 4-week period. However, participants could be down-titrated to alleviate any MET-related tolerability issues.
Adjusted Change in Femoral Neck (FN) Infero-anterior Cortical Thickness Via QCT From Week 52 + 30 Days to Week 76 + 30 Days	0.09 millimeters Standard Error 0.065	0.01 millimeters Standard Error 0.078

POST_HOC outcome

Timeframe: Baseline, Week 52, and Week 76

Population: Safety Population. Only evaluable participants with a value at Baseline and at Week 52 or Week 76 for the parameter of interest were analyzed.

AASC levels were measured from blood samples. AASC is the amount of free calcium circulating in the blood and calcium is required for good bone health. Change from baseline was calculated as the Week 52or Week 76 value minus the baseline value and was assessed by an ANCOVA with terms for treatment, baseline value, prior therapy, and region.

Outcome measures

Outcome measures
Measure	Rosiglitazone in DB Period; Metformin in OL Period n=73 Participants Rosiglitazone (RSG) initiated at a total daily dose of 4 milligrams (mg) in the 52-week DB Period. RSG could be uptitrated to a total daily dose of 8 mg at Week 4. At Week 52, all participants were switched to open-label (OL) Metformin (MET) therapy for 24 weeks during the follow-up phase; all participants were force-titrated from 1000 mg/day to 2000 mg/day over a 4-week period. However, participants could be down-titrated to alleviate any MET-related tolerability issues.	Metformin in DB Period; Metformin in OL Period n=83 Participants Metformin (MET) initiated at a total daily dose of 1000 mg in the 52-week DB Period. MET could be uptitrated to 1500 mg/day at Week 2 and to 2000 mg/day at Week 4. At Week 52, all participants were switched to open-label MET therapy for 24 weeks during the follow-up phase; all participants were force-titrated from 1000 mg/day to 2000 mg/day over a 4-week period. However, participants could be down-titrated to alleviate any MET-related tolerability issues.
Adjusted Change From Baseline in Albumin-adjusted Serum Calcium (AASC) at Week 52 and Week 76 Week 52, n=73, 83	0.01 millimoles per Liter (mmol/L) Standard Error 0.009	0.03 millimoles per Liter (mmol/L) Standard Error 0.009
Adjusted Change From Baseline in Albumin-adjusted Serum Calcium (AASC) at Week 52 and Week 76 Week 76, n=64, 75	0.03 millimoles per Liter (mmol/L) Standard Error 0.010	0.04 millimoles per Liter (mmol/L) Standard Error 0.010

POST_HOC outcome

Timeframe: Week 52 and Week 76

Population: Safety Population. Only evaluable participants with a value at Week 52 and at Week 76 for the parameter of interest were analyzed.

AASC levels were measured from blood samples. AASC is the amount of free calcium circulating in the blood and calcium is required for good bone health. Change from Week 52 was calculated as the Week 76 value minus the Week 52 value and was assessed by an ANCOVA with terms for treatment, baseline value, prior therapy, and region.

Outcome measures

Outcome measures
Measure	Rosiglitazone in DB Period; Metformin in OL Period n=64 Participants Rosiglitazone (RSG) initiated at a total daily dose of 4 milligrams (mg) in the 52-week DB Period. RSG could be uptitrated to a total daily dose of 8 mg at Week 4. At Week 52, all participants were switched to open-label (OL) Metformin (MET) therapy for 24 weeks during the follow-up phase; all participants were force-titrated from 1000 mg/day to 2000 mg/day over a 4-week period. However, participants could be down-titrated to alleviate any MET-related tolerability issues.	Metformin in DB Period; Metformin in OL Period n=74 Participants Metformin (MET) initiated at a total daily dose of 1000 mg in the 52-week DB Period. MET could be uptitrated to 1500 mg/day at Week 2 and to 2000 mg/day at Week 4. At Week 52, all participants were switched to open-label MET therapy for 24 weeks during the follow-up phase; all participants were force-titrated from 1000 mg/day to 2000 mg/day over a 4-week period. However, participants could be down-titrated to alleviate any MET-related tolerability issues.
Adjusted Change in Albumin-adjusted Serum Calcium (AASC) From Week 52 to Week 76	0.01 millimoles per Liter (mmol/L) Standard Error 0.011	0.00 millimoles per Liter (mmol/L) Standard Error 0.010

Adverse Events

Rosiglitazone: DB

Serious events: 7 serious events

Other events: 47 other events

Deaths: 0 deaths

Metformin: DB

Serious events: 5 serious events

Other events: 45 other events

Deaths: 0 deaths

Rosiglitazone: MET OL

Serious events: 0 serious events

Other events: 12 other events

Deaths: 0 deaths

Metformin: MET OL

Serious events: 0 serious events

Other events: 8 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Rosiglitazone: DB n=115 participants at risk；n=114 participants at risk Rosiglitazone (RSG) initiated at a total daily dose of 4 milligrams (mg). RSG could be uptitrated to a total daily dose of 8 mg at Week 4 in the 52-week Double-Blind (DB) Period.	Metformin: DB n=111 participants at risk Metformin (MET) initiated at a total daily dose of 1000 mg. MET could be uptitrated to 1500 mg/day at Week 2 and to 2000 mg/day at Week 4 in the 52-week DB Period.	Rosiglitazone: MET OL n=76 participants at risk At Week 52, all participants receiving RSG in the DB Period were switched to open-label Metformin (MET) therapy for 24 weeks during the Open-label (OL) Period; all participants were force-titrated from 1000 mg/day to 2000 mg/day over a 4-week period. However, participants could be down-titrated to alleviate any MET-related tolerability issues.	Metformin: MET OL n=84 participants at risk At Week 52, all participants receiving MET in the DB Period were switched to open-label MET therapy for 24 weeks during the OL Period; all participants were force-titrated from 1000 mg/day to 2000 mg/day over a 4-week period. However, participants could be down-titrated to alleviate any MET-related tolerability issues.
Gastrointestinal disorders Diarrhoea	2.6% 3/115 • 76 weeks Serious adverse events (SAEs) and AEs were collected in the Safety Population, comprised of all randomized participants who received at least one dose of study medication.	13.5% 15/111 • 76 weeks Serious adverse events (SAEs) and AEs were collected in the Safety Population, comprised of all randomized participants who received at least one dose of study medication.	7.9% 6/76 • 76 weeks Serious adverse events (SAEs) and AEs were collected in the Safety Population, comprised of all randomized participants who received at least one dose of study medication.	1.2% 1/84 • 76 weeks Serious adverse events (SAEs) and AEs were collected in the Safety Population, comprised of all randomized participants who received at least one dose of study medication.
Gastrointestinal disorders Dyspepsia	1.7% 2/115 • 76 weeks Serious adverse events (SAEs) and AEs were collected in the Safety Population, comprised of all randomized participants who received at least one dose of study medication.	5.4% 6/111 • 76 weeks Serious adverse events (SAEs) and AEs were collected in the Safety Population, comprised of all randomized participants who received at least one dose of study medication.	0.00% 0/76 • 76 weeks Serious adverse events (SAEs) and AEs were collected in the Safety Population, comprised of all randomized participants who received at least one dose of study medication.	0.00% 0/84 • 76 weeks Serious adverse events (SAEs) and AEs were collected in the Safety Population, comprised of all randomized participants who received at least one dose of study medication.
General disorders Oedemal peripheral	14.8% 17/115 • 76 weeks Serious adverse events (SAEs) and AEs were collected in the Safety Population, comprised of all randomized participants who received at least one dose of study medication.	0.00% 0/111 • 76 weeks Serious adverse events (SAEs) and AEs were collected in the Safety Population, comprised of all randomized participants who received at least one dose of study medication.	0.00% 0/76 • 76 weeks Serious adverse events (SAEs) and AEs were collected in the Safety Population, comprised of all randomized participants who received at least one dose of study medication.	0.00% 0/84 • 76 weeks Serious adverse events (SAEs) and AEs were collected in the Safety Population, comprised of all randomized participants who received at least one dose of study medication.
General disorders Fatigue	5.2% 6/115 • 76 weeks Serious adverse events (SAEs) and AEs were collected in the Safety Population, comprised of all randomized participants who received at least one dose of study medication.	3.6% 4/111 • 76 weeks Serious adverse events (SAEs) and AEs were collected in the Safety Population, comprised of all randomized participants who received at least one dose of study medication.	0.00% 0/76 • 76 weeks Serious adverse events (SAEs) and AEs were collected in the Safety Population, comprised of all randomized participants who received at least one dose of study medication.	0.00% 0/84 • 76 weeks Serious adverse events (SAEs) and AEs were collected in the Safety Population, comprised of all randomized participants who received at least one dose of study medication.
Infections and infestations Nasopharyngitis	6.1% 7/115 • 76 weeks Serious adverse events (SAEs) and AEs were collected in the Safety Population, comprised of all randomized participants who received at least one dose of study medication.	6.3% 7/111 • 76 weeks Serious adverse events (SAEs) and AEs were collected in the Safety Population, comprised of all randomized participants who received at least one dose of study medication.	1.3% 1/76 • 76 weeks Serious adverse events (SAEs) and AEs were collected in the Safety Population, comprised of all randomized participants who received at least one dose of study medication.	0.00% 0/84 • 76 weeks Serious adverse events (SAEs) and AEs were collected in the Safety Population, comprised of all randomized participants who received at least one dose of study medication.
Infections and infestations Influenza	2.6% 3/115 • 76 weeks Serious adverse events (SAEs) and AEs were collected in the Safety Population, comprised of all randomized participants who received at least one dose of study medication.	5.4% 6/111 • 76 weeks Serious adverse events (SAEs) and AEs were collected in the Safety Population, comprised of all randomized participants who received at least one dose of study medication.	0.00% 0/76 • 76 weeks Serious adverse events (SAEs) and AEs were collected in the Safety Population, comprised of all randomized participants who received at least one dose of study medication.	1.2% 1/84 • 76 weeks Serious adverse events (SAEs) and AEs were collected in the Safety Population, comprised of all randomized participants who received at least one dose of study medication.
Musculoskeletal and connective tissue disorders Arthralgia	4.3% 5/115 • 76 weeks Serious adverse events (SAEs) and AEs were collected in the Safety Population, comprised of all randomized participants who received at least one dose of study medication.	5.4% 6/111 • 76 weeks Serious adverse events (SAEs) and AEs were collected in the Safety Population, comprised of all randomized participants who received at least one dose of study medication.	1.3% 1/76 • 76 weeks Serious adverse events (SAEs) and AEs were collected in the Safety Population, comprised of all randomized participants who received at least one dose of study medication.	0.00% 0/84 • 76 weeks Serious adverse events (SAEs) and AEs were collected in the Safety Population, comprised of all randomized participants who received at least one dose of study medication.
Musculoskeletal and connective tissue disorders Back pain	5.2% 6/115 • 76 weeks Serious adverse events (SAEs) and AEs were collected in the Safety Population, comprised of all randomized participants who received at least one dose of study medication.	4.5% 5/111 • 76 weeks Serious adverse events (SAEs) and AEs were collected in the Safety Population, comprised of all randomized participants who received at least one dose of study medication.	1.3% 1/76 • 76 weeks Serious adverse events (SAEs) and AEs were collected in the Safety Population, comprised of all randomized participants who received at least one dose of study medication.	0.00% 0/84 • 76 weeks Serious adverse events (SAEs) and AEs were collected in the Safety Population, comprised of all randomized participants who received at least one dose of study medication.
Nervous system disorders Headache	7.8% 9/115 • 76 weeks Serious adverse events (SAEs) and AEs were collected in the Safety Population, comprised of all randomized participants who received at least one dose of study medication.	4.5% 5/111 • 76 weeks Serious adverse events (SAEs) and AEs were collected in the Safety Population, comprised of all randomized participants who received at least one dose of study medication.	1.3% 1/76 • 76 weeks Serious adverse events (SAEs) and AEs were collected in the Safety Population, comprised of all randomized participants who received at least one dose of study medication.	1.2% 1/84 • 76 weeks Serious adverse events (SAEs) and AEs were collected in the Safety Population, comprised of all randomized participants who received at least one dose of study medication.
Investigations Weight increased	7.8% 9/115 • 76 weeks Serious adverse events (SAEs) and AEs were collected in the Safety Population, comprised of all randomized participants who received at least one dose of study medication.	0.90% 1/111 • 76 weeks Serious adverse events (SAEs) and AEs were collected in the Safety Population, comprised of all randomized participants who received at least one dose of study medication.	0.00% 0/76 • 76 weeks Serious adverse events (SAEs) and AEs were collected in the Safety Population, comprised of all randomized participants who received at least one dose of study medication.	0.00% 0/84 • 76 weeks Serious adverse events (SAEs) and AEs were collected in the Safety Population, comprised of all randomized participants who received at least one dose of study medication.
Respiratory, thoracic and mediastinal disorders Cough	5.2% 6/115 • 76 weeks Serious adverse events (SAEs) and AEs were collected in the Safety Population, comprised of all randomized participants who received at least one dose of study medication.	0.90% 1/111 • 76 weeks Serious adverse events (SAEs) and AEs were collected in the Safety Population, comprised of all randomized participants who received at least one dose of study medication.	1.3% 1/76 • 76 weeks Serious adverse events (SAEs) and AEs were collected in the Safety Population, comprised of all randomized participants who received at least one dose of study medication.	1.2% 1/84 • 76 weeks Serious adverse events (SAEs) and AEs were collected in the Safety Population, comprised of all randomized participants who received at least one dose of study medication.
Gastrointestinal disorders Nausea	2.6% 3/115 • 76 weeks Serious adverse events (SAEs) and AEs were collected in the Safety Population, comprised of all randomized participants who received at least one dose of study medication.	2.7% 3/111 • 76 weeks Serious adverse events (SAEs) and AEs were collected in the Safety Population, comprised of all randomized participants who received at least one dose of study medication.	3.9% 3/76 • 76 weeks Serious adverse events (SAEs) and AEs were collected in the Safety Population, comprised of all randomized participants who received at least one dose of study medication.	6.0% 5/84 • 76 weeks Serious adverse events (SAEs) and AEs were collected in the Safety Population, comprised of all randomized participants who received at least one dose of study medication.

Additional Information

GSK Response Center

GlaxoSmithKline

Phone: 866-435-7343

Results disclosure agreements

Principal investigator is a sponsor employee GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
Publication restrictions are in place

Restriction type: OTHER

Measure	Rosiglitazone: DB n=115 participants at risk；n=114 participants at risk Rosiglitazone (RSG) initiated at a total daily dose of 4 milligrams (mg). RSG could be uptitrated to a total daily dose of 8 mg at Week 4 in the 52-week Double-Blind (DB) Period.	Metformin: DB n=111 participants at risk Metformin (MET) initiated at a total daily dose of 1000 mg. MET could be uptitrated to 1500 mg/day at Week 2 and to 2000 mg/day at Week 4 in the 52-week DB Period.	Rosiglitazone: MET OL n=76 participants at risk At Week 52, all participants receiving RSG in the DB Period were switched to open-label Metformin (MET) therapy for 24 weeks during the Open-label (OL) Period; all participants were force-titrated from 1000 mg/day to 2000 mg/day over a 4-week period. However, participants could be down-titrated to alleviate any MET-related tolerability issues.	Metformin: MET OL n=84 participants at risk At Week 52, all participants receiving MET in the DB Period were switched to open-label MET therapy for 24 weeks during the OL Period; all participants were force-titrated from 1000 mg/day to 2000 mg/day over a 4-week period. However, participants could be down-titrated to alleviate any MET-related tolerability issues.
General disorders Device dislocation	0.88% 1/114 • 76 weeks Serious adverse events (SAEs) and AEs were collected in the Safety Population, comprised of all randomized participants who received at least one dose of study medication.	0.00% 0/111 • 76 weeks Serious adverse events (SAEs) and AEs were collected in the Safety Population, comprised of all randomized participants who received at least one dose of study medication.	0.00% 0/76 • 76 weeks Serious adverse events (SAEs) and AEs were collected in the Safety Population, comprised of all randomized participants who received at least one dose of study medication.	0.00% 0/84 • 76 weeks Serious adverse events (SAEs) and AEs were collected in the Safety Population, comprised of all randomized participants who received at least one dose of study medication.
General disorders Generalised oedema	0.88% 1/114 • 76 weeks Serious adverse events (SAEs) and AEs were collected in the Safety Population, comprised of all randomized participants who received at least one dose of study medication.	0.00% 0/111 • 76 weeks Serious adverse events (SAEs) and AEs were collected in the Safety Population, comprised of all randomized participants who received at least one dose of study medication.	0.00% 0/76 • 76 weeks Serious adverse events (SAEs) and AEs were collected in the Safety Population, comprised of all randomized participants who received at least one dose of study medication.	0.00% 0/84 • 76 weeks Serious adverse events (SAEs) and AEs were collected in the Safety Population, comprised of all randomized participants who received at least one dose of study medication.
General disorders Sudden cardiac death	0.88% 1/114 • 76 weeks Serious adverse events (SAEs) and AEs were collected in the Safety Population, comprised of all randomized participants who received at least one dose of study medication.	0.00% 0/111 • 76 weeks Serious adverse events (SAEs) and AEs were collected in the Safety Population, comprised of all randomized participants who received at least one dose of study medication.	0.00% 0/76 • 76 weeks Serious adverse events (SAEs) and AEs were collected in the Safety Population, comprised of all randomized participants who received at least one dose of study medication.	0.00% 0/84 • 76 weeks Serious adverse events (SAEs) and AEs were collected in the Safety Population, comprised of all randomized participants who received at least one dose of study medication.
Infections and infestations Urinary tract infection	0.88% 1/114 • 76 weeks Serious adverse events (SAEs) and AEs were collected in the Safety Population, comprised of all randomized participants who received at least one dose of study medication.	0.90% 1/111 • 76 weeks Serious adverse events (SAEs) and AEs were collected in the Safety Population, comprised of all randomized participants who received at least one dose of study medication.	0.00% 0/76 • 76 weeks Serious adverse events (SAEs) and AEs were collected in the Safety Population, comprised of all randomized participants who received at least one dose of study medication.	0.00% 0/84 • 76 weeks Serious adverse events (SAEs) and AEs were collected in the Safety Population, comprised of all randomized participants who received at least one dose of study medication.
Infections and infestations Enteritis infectious	0.00% 0/114 • 76 weeks Serious adverse events (SAEs) and AEs were collected in the Safety Population, comprised of all randomized participants who received at least one dose of study medication.	0.90% 1/111 • 76 weeks Serious adverse events (SAEs) and AEs were collected in the Safety Population, comprised of all randomized participants who received at least one dose of study medication.	0.00% 0/76 • 76 weeks Serious adverse events (SAEs) and AEs were collected in the Safety Population, comprised of all randomized participants who received at least one dose of study medication.	0.00% 0/84 • 76 weeks Serious adverse events (SAEs) and AEs were collected in the Safety Population, comprised of all randomized participants who received at least one dose of study medication.
Infections and infestations Escherichia infection	0.88% 1/114 • 76 weeks Serious adverse events (SAEs) and AEs were collected in the Safety Population, comprised of all randomized participants who received at least one dose of study medication.	0.00% 0/111 • 76 weeks Serious adverse events (SAEs) and AEs were collected in the Safety Population, comprised of all randomized participants who received at least one dose of study medication.	0.00% 0/76 • 76 weeks Serious adverse events (SAEs) and AEs were collected in the Safety Population, comprised of all randomized participants who received at least one dose of study medication.	0.00% 0/84 • 76 weeks Serious adverse events (SAEs) and AEs were collected in the Safety Population, comprised of all randomized participants who received at least one dose of study medication.
Infections and infestations Pyelonephritis	0.88% 1/114 • 76 weeks Serious adverse events (SAEs) and AEs were collected in the Safety Population, comprised of all randomized participants who received at least one dose of study medication.	0.00% 0/111 • 76 weeks Serious adverse events (SAEs) and AEs were collected in the Safety Population, comprised of all randomized participants who received at least one dose of study medication.	0.00% 0/76 • 76 weeks Serious adverse events (SAEs) and AEs were collected in the Safety Population, comprised of all randomized participants who received at least one dose of study medication.	0.00% 0/84 • 76 weeks Serious adverse events (SAEs) and AEs were collected in the Safety Population, comprised of all randomized participants who received at least one dose of study medication.
Nervous system disorders Cerebral infarction	0.00% 0/114 • 76 weeks Serious adverse events (SAEs) and AEs were collected in the Safety Population, comprised of all randomized participants who received at least one dose of study medication.	0.90% 1/111 • 76 weeks Serious adverse events (SAEs) and AEs were collected in the Safety Population, comprised of all randomized participants who received at least one dose of study medication.	0.00% 0/76 • 76 weeks Serious adverse events (SAEs) and AEs were collected in the Safety Population, comprised of all randomized participants who received at least one dose of study medication.	0.00% 0/84 • 76 weeks Serious adverse events (SAEs) and AEs were collected in the Safety Population, comprised of all randomized participants who received at least one dose of study medication.
Nervous system disorders Presyncope	0.88% 1/114 • 76 weeks Serious adverse events (SAEs) and AEs were collected in the Safety Population, comprised of all randomized participants who received at least one dose of study medication.	0.00% 0/111 • 76 weeks Serious adverse events (SAEs) and AEs were collected in the Safety Population, comprised of all randomized participants who received at least one dose of study medication.	0.00% 0/76 • 76 weeks Serious adverse events (SAEs) and AEs were collected in the Safety Population, comprised of all randomized participants who received at least one dose of study medication.	0.00% 0/84 • 76 weeks Serious adverse events (SAEs) and AEs were collected in the Safety Population, comprised of all randomized participants who received at least one dose of study medication.
Respiratory, thoracic and mediastinal disorders Asthma	0.00% 0/114 • 76 weeks Serious adverse events (SAEs) and AEs were collected in the Safety Population, comprised of all randomized participants who received at least one dose of study medication.	0.90% 1/111 • 76 weeks Serious adverse events (SAEs) and AEs were collected in the Safety Population, comprised of all randomized participants who received at least one dose of study medication.	0.00% 0/76 • 76 weeks Serious adverse events (SAEs) and AEs were collected in the Safety Population, comprised of all randomized participants who received at least one dose of study medication.	0.00% 0/84 • 76 weeks Serious adverse events (SAEs) and AEs were collected in the Safety Population, comprised of all randomized participants who received at least one dose of study medication.
Respiratory, thoracic and mediastinal disorders Pleural effusion	0.88% 1/114 • 76 weeks Serious adverse events (SAEs) and AEs were collected in the Safety Population, comprised of all randomized participants who received at least one dose of study medication.	0.00% 0/111 • 76 weeks Serious adverse events (SAEs) and AEs were collected in the Safety Population, comprised of all randomized participants who received at least one dose of study medication.	0.00% 0/76 • 76 weeks Serious adverse events (SAEs) and AEs were collected in the Safety Population, comprised of all randomized participants who received at least one dose of study medication.	0.00% 0/84 • 76 weeks Serious adverse events (SAEs) and AEs were collected in the Safety Population, comprised of all randomized participants who received at least one dose of study medication.
Cardiac disorders Coronary artery disease	0.00% 0/114 • 76 weeks Serious adverse events (SAEs) and AEs were collected in the Safety Population, comprised of all randomized participants who received at least one dose of study medication.	0.90% 1/111 • 76 weeks Serious adverse events (SAEs) and AEs were collected in the Safety Population, comprised of all randomized participants who received at least one dose of study medication.	0.00% 0/76 • 76 weeks Serious adverse events (SAEs) and AEs were collected in the Safety Population, comprised of all randomized participants who received at least one dose of study medication.	0.00% 0/84 • 76 weeks Serious adverse events (SAEs) and AEs were collected in the Safety Population, comprised of all randomized participants who received at least one dose of study medication.
Gastrointestinal disorders Umbilical hernia, obstructive	0.88% 1/114 • 76 weeks Serious adverse events (SAEs) and AEs were collected in the Safety Population, comprised of all randomized participants who received at least one dose of study medication.	0.00% 0/111 • 76 weeks Serious adverse events (SAEs) and AEs were collected in the Safety Population, comprised of all randomized participants who received at least one dose of study medication.	0.00% 0/76 • 76 weeks Serious adverse events (SAEs) and AEs were collected in the Safety Population, comprised of all randomized participants who received at least one dose of study medication.	0.00% 0/84 • 76 weeks Serious adverse events (SAEs) and AEs were collected in the Safety Population, comprised of all randomized participants who received at least one dose of study medication.
Injury, poisoning and procedural complications Wrist fracture	0.00% 0/114 • 76 weeks Serious adverse events (SAEs) and AEs were collected in the Safety Population, comprised of all randomized participants who received at least one dose of study medication.	0.90% 1/111 • 76 weeks Serious adverse events (SAEs) and AEs were collected in the Safety Population, comprised of all randomized participants who received at least one dose of study medication.	0.00% 0/76 • 76 weeks Serious adverse events (SAEs) and AEs were collected in the Safety Population, comprised of all randomized participants who received at least one dose of study medication.	0.00% 0/84 • 76 weeks Serious adverse events (SAEs) and AEs were collected in the Safety Population, comprised of all randomized participants who received at least one dose of study medication.
Investigations Alanine aminotransferase increased	0.00% 0/114 • 76 weeks Serious adverse events (SAEs) and AEs were collected in the Safety Population, comprised of all randomized participants who received at least one dose of study medication.	0.90% 1/111 • 76 weeks Serious adverse events (SAEs) and AEs were collected in the Safety Population, comprised of all randomized participants who received at least one dose of study medication.	0.00% 0/76 • 76 weeks Serious adverse events (SAEs) and AEs were collected in the Safety Population, comprised of all randomized participants who received at least one dose of study medication.	0.00% 0/84 • 76 weeks Serious adverse events (SAEs) and AEs were collected in the Safety Population, comprised of all randomized participants who received at least one dose of study medication.
Vascular disorders Hypertension	0.88% 1/114 • 76 weeks Serious adverse events (SAEs) and AEs were collected in the Safety Population, comprised of all randomized participants who received at least one dose of study medication.	0.00% 0/111 • 76 weeks Serious adverse events (SAEs) and AEs were collected in the Safety Population, comprised of all randomized participants who received at least one dose of study medication.	0.00% 0/76 • 76 weeks Serious adverse events (SAEs) and AEs were collected in the Safety Population, comprised of all randomized participants who received at least one dose of study medication.	0.00% 0/84 • 76 weeks Serious adverse events (SAEs) and AEs were collected in the Safety Population, comprised of all randomized participants who received at least one dose of study medication.