Trial Outcomes & Findings for Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) (NCT NCT00081328)

Last Updated: 2021-07-30

Results Overview

Defined as A1c persistently \>=8% over a 6-month period or persistent metabolic decompensation (inability to wean insulin within 3 months of initiation or the occurrence of a second episode within three months of discontinuing insulin)

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

699 participants

Primary outcome timeframe

Study duration - 2 years to 6.5 years of follow up from randomization

Results posted on

2021-07-30

Participant Flow

Participants were recruited from July 2004 to February 2009. Participants were recruited from the patient populations of pediatric endocrine clinics at the participating study clinical centers, including satellite clinics. Posters announced the study. Study staff approached youth and their families during medical visits.

Prior to randomization, eligible subjects entered a 2-6 month run-in period, with goals of weaning from non-study diabetes medications, tolerating metformin at 1000 mg bid but no less than 500 mg bid, attaining glycemic control on metformin alone, mastering standard diabetes education, and adhering to study medication and visit attendance.

Participant milestones

Participant milestones
Measure	1 Metformin Alone Metformin alone Metformin: capsule, 1000 mg bid, provided encapsulated in weekly packets	2 Metformin + Rosliglitazone Metformin + Rosiglitazone Metformin: capsule, 1000 mg bid Rosiglitazone: capsule, 4 mg bid, provided encapsulated in weekly packets	3 Metformin + Lifestyle Program Metformin + Lifestyle Program Metformin: capsule, 1000 mg bid, encapsulated, provided in weekly packets Lifestyle Program: a lifestyle change (LC) phase of weekly sessions for months 1-6, followed by a bi-weekly lifestyle maintenance (LM) phase through months 7-12, and a continued contact (CC) phase from months 13 through the end of the study. The CC phase sessions are scheduled monthly for the initial 12 months (study months 13-24) and then quarterly or 4 times a year to the end of the study
Overall Study STARTED	232	233	234
Overall Study COMPLETED	232	233	234
Overall Study NOT COMPLETED	0	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	1 Metformin Alone n=232 Participants Metformin alone Metformin: capsule, 1000 mg bid	2 Metformin + Rosiglitazone n=233 Participants Metformin + Rosiglitazone Metformin: capsule, 1000 mg bid Rosiglitazone: capsule, 4 mg bid	3 Metformin + Lifestyle Program n=234 Participants Metformin + Lifestyle Program Metformin: capsule, 1000 mg bid Lifestyle Program: a lifestyle change (LC) phase of weekly sessions for months 1-6, followed by a bi-weekly lifestyle maintenance (LM) phase through months 7-12, and a continued contact (CC) phase from months 13 through the end of the study. The CC phase sessions are scheduled monthly for the initial 12 months (study months 13-24) and then quarterly or 4 times a year to the end of the study	Total n=699 Participants Total of all reporting groups
Age, Continuous	14.1 years STANDARD_DEVIATION 1.9 • n=39 Participants	14.1 years STANDARD_DEVIATION 2.1 • n=41 Participants	13.8 years STANDARD_DEVIATION 2.0 • n=35 Participants	14.0 years STANDARD_DEVIATION 2.0 • n=31 Participants
Sex: Female, Male Female	146 Participants n=39 Participants	152 Participants n=41 Participants	154 Participants n=35 Participants	452 Participants n=31 Participants
Sex: Female, Male Male	86 Participants n=39 Participants	81 Participants n=41 Participants	80 Participants n=35 Participants	247 Participants n=31 Participants
Race/Ethnicity, Customized American Indian	12 participants n=39 Participants	16 participants n=41 Participants	13 participants n=35 Participants	41 participants n=31 Participants
Race/Ethnicity, Customized Black Non-Hispanic	77 participants n=39 Participants	64 participants n=41 Participants	86 participants n=35 Participants	227 participants n=31 Participants
Race/Ethnicity, Customized Hispanic	91 participants n=39 Participants	101 participants n=41 Participants	86 participants n=35 Participants	278 participants n=31 Participants
Race/Ethnicity, Customized White Non-Hispanic	49 participants n=39 Participants	47 participants n=41 Participants	46 participants n=35 Participants	142 participants n=31 Participants
Race/Ethnicity, Customized Asian Non-Hispanic	3 participants n=39 Participants	5 participants n=41 Participants	3 participants n=35 Participants	11 participants n=31 Participants
Region of Enrollment United States	232 participants n=39 Participants	233 participants n=41 Participants	234 participants n=35 Participants	699 participants n=31 Participants
Body mass index z-score	2.27 z-score STANDARD_DEVIATION 0.45 • n=39 Participants	2.22 z-score STANDARD_DEVIATION 0.49 • n=41 Participants	2.18 z-score STANDARD_DEVIATION 0.46 • n=35 Participants	2.23 z-score STANDARD_DEVIATION 0.47 • n=31 Participants
Percent overweight	82.1 100% X (BMI-50th %ile)/50th %ile STANDARD_DEVIATION 38.3 • n=39 Participants	79.1 100% X (BMI-50th %ile)/50th %ile STANDARD_DEVIATION 38.1 • n=41 Participants	75.6 100% X (BMI-50th %ile)/50th %ile STANDARD_DEVIATION 35.3 • n=35 Participants	78.9 100% X (BMI-50th %ile)/50th %ile STANDARD_DEVIATION 37.3 • n=31 Participants
Duration of diabetes	7.8 months STANDARD_DEVIATION 6.0 • n=39 Participants	8.0 months STANDARD_DEVIATION 5.7 • n=41 Participants	7.6 months STANDARD_DEVIATION 5.8 • n=35 Participants	7.8 months STANDARD_DEVIATION 5.8 • n=31 Participants
Total annual household income < $25,000	81 participants n=39 Participants	86 participants n=41 Participants	92 participants n=35 Participants	259 participants n=31 Participants
Total annual household income $25,000-49,999	83 participants n=39 Participants	61 participants n=41 Participants	66 participants n=35 Participants	210 participants n=31 Participants
Total annual household income >=$50,000	44 participants n=39 Participants	58 participants n=41 Participants	53 participants n=35 Participants	155 participants n=31 Participants
Total annual household income unknown	24 participants n=39 Participants	28 participants n=41 Participants	23 participants n=35 Participants	75 participants n=31 Participants
Highest household education level Less than high school	60 participants n=39 Participants	60 participants n=41 Participants	62 participants n=35 Participants	182 participants n=31 Participants
Highest household education level High school, GED, business or technical	57 participants n=39 Participants	49 participants n=41 Participants	66 participants n=35 Participants	172 participants n=31 Participants
Highest household education level College no degree	77 participants n=39 Participants	78 participants n=41 Participants	63 participants n=35 Participants	218 participants n=31 Participants
Highest household education level Graduate degree	35 participants n=39 Participants	41 participants n=41 Participants	38 participants n=35 Participants	114 participants n=31 Participants
Highest household education level Unknown	3 participants n=39 Participants	5 participants n=41 Participants	5 participants n=35 Participants	13 participants n=31 Participants
Tanner stage by physical examination 4 or 5	209 participants n=39 Participants	207 participants n=41 Participants	204 participants n=35 Participants	620 participants n=31 Participants
Tanner stage by physical examination 1, 2, or 3	23 participants n=39 Participants	26 participants n=41 Participants	30 participants n=35 Participants	79 participants n=31 Participants
Nuclear family history of diabetes No	97 participants n=39 Participants	93 participants n=41 Participants	86 participants n=35 Participants	276 participants n=31 Participants
Nuclear family history of diabetes Yes	131 participants n=39 Participants	133 participants n=41 Participants	143 participants n=35 Participants	407 participants n=31 Participants
Nuclear family history of diabetes Unknown	4 participants n=39 Participants	7 participants n=41 Participants	5 participants n=35 Participants	16 participants n=31 Participants
Nuclear family + grandparents history of diabetes No	17 participants n=39 Participants	26 participants n=41 Participants	29 participants n=35 Participants	72 participants n=31 Participants
Nuclear family + grandparents history of diabetes Yes	211 participants n=39 Participants	200 participants n=41 Participants	200 participants n=35 Participants	611 participants n=31 Participants
Nuclear family + grandparents history of diabetes Unknown	4 participants n=39 Participants	7 participants n=41 Participants	5 participants n=35 Participants	16 participants n=31 Participants
Insulin sensitivity (inverse of fasting insulin from OGTT)	.036 mL/uU n=39 Participants	.040 mL/uU n=41 Participants	.040 mL/uU n=35 Participants	.039 mL/uU n=31 Participants
Insulinogenic index from OGTT	1.02 uU/mL divided by mg/dL n=39 Participants	.92 uU/mL divided by mg/dL n=41 Participants	.87 uU/mL divided by mg/dL n=35 Participants	.93 uU/mL divided by mg/dL n=31 Participants
Body mass index (BMI)	35.8 kg per m squared STANDARD_DEVIATION 8.1 • n=39 Participants	35.0 kg per m squared STANDARD_DEVIATION 7.7 • n=41 Participants	34.1 kg per m squared STANDARD_DEVIATION 7.1 • n=35 Participants	34.9 kg per m squared STANDARD_DEVIATION 7.6 • n=31 Participants
Waist circumference	110.4 cm STANDARD_DEVIATION 16.6 • n=39 Participants	109.0 cm STANDARD_DEVIATION 17.0 • n=41 Participants	106.6 cm STANDARD_DEVIATION 16.2 • n=35 Participants	108.6 cm STANDARD_DEVIATION 16.7 • n=31 Participants
Fat mass from DXA	33.7 kg STANDARD_DEVIATION 9.9 • n=39 Participants	33.5 kg STANDARD_DEVIATION 10.2 • n=41 Participants	32.6 kg STANDARD_DEVIATION 9.8 • n=35 Participants	33.3 kg STANDARD_DEVIATION 10.0 • n=31 Participants
Bone density from DXA	1.09 g per cm squared STANDARD_DEVIATION .12 • n=39 Participants	1.10 g per cm squared STANDARD_DEVIATION .13 • n=41 Participants	1.08 g per cm squared STANDARD_DEVIATION .12 • n=35 Participants	1.09 g per cm squared STANDARD_DEVIATION .13 • n=31 Participants

PRIMARY outcome

Timeframe: Study duration - 2 years to 6.5 years of follow up from randomization

Population: The entire cohort of 699 participants was included in the analysis.

Outcome measures

Outcome measures
Measure	1 Metformin Alone n=232 Participants Metformin alone Metformin: capsule, 1000 mg bid	2 Metformin + Rosliglitazone n=233 Participants Metformin + Rosiglitazone Metformin: capsule, 1000 mg bid Rosiglitazone: capsule, 4 mg bid	3 Metformin + Lifestyle Program n=234 Participants Metformin + Lifestyle Program Metformin: capsule, 1000 mg bid Lifestyle Program: a lifestyle change (LC) phase of weekly sessions for months 1-6, followed by a bi-weekly lifestyle maintenance (LM) phase through months 7-12, and a continued contact (CC) phase from months 13 through the end of the study. The CC phase sessions are scheduled monthly for the initial 12 months (study months 13-24) and then quarterly or 4 times a year to the end of the study
Treatment Failure (Loss of Glycemic Control) Treatment failure	120 participants	90 participants	109 participants
Treatment Failure (Loss of Glycemic Control) Did not fail treatment during trial	112 participants	143 participants	125 participants

SECONDARY outcome

Timeframe: 24 months

Population: Participants who were measured at 24 months and had not experienced treatment failure.

All participants were followed to 24 months. Insulin sensitivity is measured from OGTT as inverse of fasting insulin (mL/uU). The analysis sample includes only participants with 24 month data who had not experienced the primary outcome by that time.

Outcome measures

Outcome measures
Measure	1 Metformin Alone n=167 Participants Metformin alone Metformin: capsule, 1000 mg bid	2 Metformin + Rosliglitazone n=157 Participants Metformin + Rosiglitazone Metformin: capsule, 1000 mg bid Rosiglitazone: capsule, 4 mg bid	3 Metformin + Lifestyle Program n=167 Participants Metformin + Lifestyle Program Metformin: capsule, 1000 mg bid Lifestyle Program: a lifestyle change (LC) phase of weekly sessions for months 1-6, followed by a bi-weekly lifestyle maintenance (LM) phase through months 7-12, and a continued contact (CC) phase from months 13 through the end of the study. The CC phase sessions are scheduled monthly for the initial 12 months (study months 13-24) and then quarterly or 4 times a year to the end of the study
Insulin Sensitivity	0.037 mL/uU Interval 0.023 to 0.061	0.049 mL/uU Interval 0.031 to 0.068	0.039 mL/uU Interval 0.027 to 0.064

SECONDARY outcome

Timeframe: Reported as occurred during study follow-up - 2 years to 6.5 years from randomization.

Population: Entire cohort.

Number of serious adverse events reported during the trial. Participant could have multiple episodes reported.

Outcome measures

Outcome measures
Measure	1 Metformin Alone n=232 Participants Metformin alone Metformin: capsule, 1000 mg bid	2 Metformin + Rosliglitazone n=233 Participants Metformin + Rosiglitazone Metformin: capsule, 1000 mg bid Rosiglitazone: capsule, 4 mg bid	3 Metformin + Lifestyle Program n=234 Participants Metformin + Lifestyle Program Metformin: capsule, 1000 mg bid Lifestyle Program: a lifestyle change (LC) phase of weekly sessions for months 1-6, followed by a bi-weekly lifestyle maintenance (LM) phase through months 7-12, and a continued contact (CC) phase from months 13 through the end of the study. The CC phase sessions are scheduled monthly for the initial 12 months (study months 13-24) and then quarterly or 4 times a year to the end of the study
Number of Serious Adverse Events	42 episodes of serious adverse event	34 episodes of serious adverse event	58 episodes of serious adverse event

SECONDARY outcome

Timeframe: 24 months

Population: Participants who were measured at 24 months and had not experience treatment failure.

Insulinogenic index determined from OGTT as difference in insulin at 30 minutes minus 0 minutes divided by difference in glucose at 30 minutes minus 0 minutes. The analysis sample includes only participants with 24 month data who had not experienced the primary outcome by that time.

Outcome measures

Outcome measures
Measure	1 Metformin Alone n=150 Participants Metformin alone Metformin: capsule, 1000 mg bid	2 Metformin + Rosliglitazone n=147 Participants Metformin + Rosiglitazone Metformin: capsule, 1000 mg bid Rosiglitazone: capsule, 4 mg bid	3 Metformin + Lifestyle Program n=155 Participants Metformin + Lifestyle Program Metformin: capsule, 1000 mg bid Lifestyle Program: a lifestyle change (LC) phase of weekly sessions for months 1-6, followed by a bi-weekly lifestyle maintenance (LM) phase through months 7-12, and a continued contact (CC) phase from months 13 through the end of the study. The CC phase sessions are scheduled monthly for the initial 12 months (study months 13-24) and then quarterly or 4 times a year to the end of the study
Insulin Secretion	.75 uU/mL divided by mg/dL Interval 0.33 to 1.39	.83 uU/mL divided by mg/dL Interval 0.28 to 1.38	.71 uU/mL divided by mg/dL Interval 0.26 to 1.69

SECONDARY outcome

Timeframe: 24 months

Population: Cohort measured at 24 months and had not experienced treatment failure.

Body mass index (BMI) measured in kg per meters squared. The analysis sample includes only participants with 24 month data who had not experienced the primary outcome by that time.

Outcome measures

Outcome measures
Measure	1 Metformin Alone n=132 Participants Metformin alone Metformin: capsule, 1000 mg bid	2 Metformin + Rosliglitazone n=138 Participants Metformin + Rosiglitazone Metformin: capsule, 1000 mg bid Rosiglitazone: capsule, 4 mg bid	3 Metformin + Lifestyle Program n=134 Participants Metformin + Lifestyle Program Metformin: capsule, 1000 mg bid Lifestyle Program: a lifestyle change (LC) phase of weekly sessions for months 1-6, followed by a bi-weekly lifestyle maintenance (LM) phase through months 7-12, and a continued contact (CC) phase from months 13 through the end of the study. The CC phase sessions are scheduled monthly for the initial 12 months (study months 13-24) and then quarterly or 4 times a year to the end of the study
Body Composition -- BMI	36.7 kg per meters squared Standard Deviation 9.1	38.2 kg per meters squared Standard Deviation 8.1	35.3 kg per meters squared Standard Deviation 8.4

SECONDARY outcome

Timeframe: 24 months

Population: Members of cohort measured at 24 months who had not experience treatment failure.

Waist circumference (cm) measured at the iliac crest at its outermost point with the measuring tape placed around the participant in a horizontal plane parallel to the floor at the mark and the measurement teken at the end of normal expiration without the tape compressing the skin. The analysis sample includes only participants with 24 month data who had not experienced the primary outcome by that time.

Outcome measures

Outcome measures
Measure	1 Metformin Alone n=132 Participants Metformin alone Metformin: capsule, 1000 mg bid	2 Metformin + Rosliglitazone n=138 Participants Metformin + Rosiglitazone Metformin: capsule, 1000 mg bid Rosiglitazone: capsule, 4 mg bid	3 Metformin + Lifestyle Program n=134 Participants Metformin + Lifestyle Program Metformin: capsule, 1000 mg bid Lifestyle Program: a lifestyle change (LC) phase of weekly sessions for months 1-6, followed by a bi-weekly lifestyle maintenance (LM) phase through months 7-12, and a continued contact (CC) phase from months 13 through the end of the study. The CC phase sessions are scheduled monthly for the initial 12 months (study months 13-24) and then quarterly or 4 times a year to the end of the study
Body Composition -- Waist Circumference	110.8 cm Standard Deviation 17.5	114.0 cm Standard Deviation 16.3	108.6 cm Standard Deviation 16.7

SECONDARY outcome

Timeframe: 24 months

Population: Members of the cohort measured at 24 months who did not experience treatment failure.

Measured by DXA, both whole body scan and AP-spine scan. The analysis sample includes only participants with 24 month data who had not experienced the primary outcome by that time. In addition, in about 1/3 of participants DXA scans could not be obtained on participants weighing more than 300 pounds (136 kg), the upper limit in size set by the machine manufacturers. Scans were considered invalid if a body part (e.g., arm, leg) was completely off or partially off the scanner, there was hand-hip overlap, or there was motion or movement during the scan.

Outcome measures

Outcome measures
Measure	1 Metformin Alone n=132 Participants Metformin alone Metformin: capsule, 1000 mg bid	2 Metformin + Rosliglitazone n=138 Participants Metformin + Rosiglitazone Metformin: capsule, 1000 mg bid Rosiglitazone: capsule, 4 mg bid	3 Metformin + Lifestyle Program n=134 Participants Metformin + Lifestyle Program Metformin: capsule, 1000 mg bid Lifestyle Program: a lifestyle change (LC) phase of weekly sessions for months 1-6, followed by a bi-weekly lifestyle maintenance (LM) phase through months 7-12, and a continued contact (CC) phase from months 13 through the end of the study. The CC phase sessions are scheduled monthly for the initial 12 months (study months 13-24) and then quarterly or 4 times a year to the end of the study
Body Composition -- Bone Density	1.15 g/cm squared Standard Deviation .10	1.15 g/cm squared Standard Deviation .11	1.15 g/cm squared Standard Deviation .12

SECONDARY outcome

Timeframe: 24 months

Population: Members of the cohort measured at 24 months who did not experience treatment failure.

Determined by DXA whole body scan. The analysis sample includes only participants with 24 month data who had not experienced the primary outcome by that time. In addition, in about 1/3 of participants DXA scans could not be obtained on participants weighing more than 300 pounds (136 kg), the upper limit in size set by the machine manufacturers. Scans were considered invalid if a body part (e.g., arm, leg) was completely off or partially off the scanner, there was hand-hip overlap, or there was motion or movement during the scan.

Outcome measures

Outcome measures
Measure	1 Metformin Alone n=132 Participants Metformin alone Metformin: capsule, 1000 mg bid	2 Metformin + Rosliglitazone n=138 Participants Metformin + Rosiglitazone Metformin: capsule, 1000 mg bid Rosiglitazone: capsule, 4 mg bid	3 Metformin + Lifestyle Program n=134 Participants Metformin + Lifestyle Program Metformin: capsule, 1000 mg bid Lifestyle Program: a lifestyle change (LC) phase of weekly sessions for months 1-6, followed by a bi-weekly lifestyle maintenance (LM) phase through months 7-12, and a continued contact (CC) phase from months 13 through the end of the study. The CC phase sessions are scheduled monthly for the initial 12 months (study months 13-24) and then quarterly or 4 times a year to the end of the study
Body Composition -- Fat Mass	36.1 kg Standard Deviation 12.0	39.7 kg Standard Deviation 10.5	32.2 kg Standard Deviation 9.4

SECONDARY outcome

Timeframe: Data collected at baseline and during follow-up - 2 years to 6.5 years from randomization.

Population: Entire cohort.

A diagnosis was made by an out-of-range value \>=95th percentile or systolic \>=130 or diastolic \>=80 sustained over 6 months or on an anti-hypertensive medication.

Outcome measures

Outcome measures
Measure	1 Metformin Alone n=232 Participants Metformin alone Metformin: capsule, 1000 mg bid	2 Metformin + Rosliglitazone n=233 Participants Metformin + Rosiglitazone Metformin: capsule, 1000 mg bid Rosiglitazone: capsule, 4 mg bid	3 Metformin + Lifestyle Program n=234 Participants Metformin + Lifestyle Program Metformin: capsule, 1000 mg bid Lifestyle Program: a lifestyle change (LC) phase of weekly sessions for months 1-6, followed by a bi-weekly lifestyle maintenance (LM) phase through months 7-12, and a continued contact (CC) phase from months 13 through the end of the study. The CC phase sessions are scheduled monthly for the initial 12 months (study months 13-24) and then quarterly or 4 times a year to the end of the study
Comorbidity -- Hypertension	57 participants	53 participants	45 participants

SECONDARY outcome

Timeframe: Data collected at baseline and during follow-up - 2 years to 6.5 years from randomization.

Population: Entire cohort.

A diagnosis was made from out-of-range value \>= 130 mg/dL sustained over 6 months or put on lipid lowering medication.

Outcome measures

Outcome measures
Measure	1 Metformin Alone n=232 Participants Metformin alone Metformin: capsule, 1000 mg bid	2 Metformin + Rosliglitazone n=233 Participants Metformin + Rosiglitazone Metformin: capsule, 1000 mg bid Rosiglitazone: capsule, 4 mg bid	3 Metformin + Lifestyle Program n=234 Participants Metformin + Lifestyle Program Metformin: capsule, 1000 mg bid Lifestyle Program: a lifestyle change (LC) phase of weekly sessions for months 1-6, followed by a bi-weekly lifestyle maintenance (LM) phase through months 7-12, and a continued contact (CC) phase from months 13 through the end of the study. The CC phase sessions are scheduled monthly for the initial 12 months (study months 13-24) and then quarterly or 4 times a year to the end of the study
Comorbidity -- LDL Dyslipidemia	18 participants	16 participants	15 participants

SECONDARY outcome

Timeframe: Data collected at baseline and during follow-up - 2 years to 6.5 years from randomization.

Population: Entire cohort.

A diagnosis was made by an out-of-range value \>=150 mg/dL sustained over 6 months or on appropriate lipid lowering medication.

Outcome measures

Outcome measures
Measure	1 Metformin Alone n=232 Participants Metformin alone Metformin: capsule, 1000 mg bid	2 Metformin + Rosliglitazone n=233 Participants Metformin + Rosiglitazone Metformin: capsule, 1000 mg bid Rosiglitazone: capsule, 4 mg bid	3 Metformin + Lifestyle Program n=234 Participants Metformin + Lifestyle Program Metformin: capsule, 1000 mg bid Lifestyle Program: a lifestyle change (LC) phase of weekly sessions for months 1-6, followed by a bi-weekly lifestyle maintenance (LM) phase through months 7-12, and a continued contact (CC) phase from months 13 through the end of the study. The CC phase sessions are scheduled monthly for the initial 12 months (study months 13-24) and then quarterly or 4 times a year to the end of the study
Comorbidity -- Triglycerides Dyslipidemia	20 participants	28 participants	22 participants

Adverse Events

1 Metformin Alone

Serious events: 42 serious events

Other events: 215 other events

Deaths: 0 deaths

2 Metformin + Rosliglitazone

Serious events: 34 serious events

Other events: 196 other events

Deaths: 0 deaths

3 Metformin + Lifestyle Program

Serious events: 58 serious events

Other events: 213 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	1 Metformin Alone n=232 participants at risk Metformin alone Metformin: capsule, 1000 mg bid	2 Metformin + Rosliglitazone n=233 participants at risk Metformin + Rosiglitazone Metformin: capsule, 1000 mg bid Rosiglitazone: capsule, 4 mg bid	3 Metformin + Lifestyle Program n=234 participants at risk Metformin + Lifestyle Program Metformin: capsule, 1000 mg bid Lifestyle Program: a lifestyle change (LC) phase of weekly sessions for months 1-6, followed by a bi-weekly lifestyle maintenance (LM) phase through months 7-12, and a continued contact (CC) phase from months 13 through the end of the study. The CC phase sessions are scheduled monthly for the initial 12 months (study months 13-24) and then quarterly or 4 times a year to the end of the study
Endocrine disorders Diabetic ketoacidosis	2.2% 5/232 • Number of events 5 • During the 2-6 month pre-randomization run-in period and during follow-up from 2-6.5 years. Terminology and criteria standard for clinical trials conducted by NIH were used.	1.3% 3/233 • Number of events 3 • During the 2-6 month pre-randomization run-in period and during follow-up from 2-6.5 years. Terminology and criteria standard for clinical trials conducted by NIH were used.	1.3% 3/234 • Number of events 3 • During the 2-6 month pre-randomization run-in period and during follow-up from 2-6.5 years. Terminology and criteria standard for clinical trials conducted by NIH were used.
Endocrine disorders Hyperglycemia	1.3% 3/232 • Number of events 3 • During the 2-6 month pre-randomization run-in period and during follow-up from 2-6.5 years. Terminology and criteria standard for clinical trials conducted by NIH were used.	2.1% 5/233 • Number of events 5 • During the 2-6 month pre-randomization run-in period and during follow-up from 2-6.5 years. Terminology and criteria standard for clinical trials conducted by NIH were used.	0.85% 2/234 • Number of events 2 • During the 2-6 month pre-randomization run-in period and during follow-up from 2-6.5 years. Terminology and criteria standard for clinical trials conducted by NIH were used.
Endocrine disorders Hypoglycemia	0.43% 1/232 • Number of events 1 • During the 2-6 month pre-randomization run-in period and during follow-up from 2-6.5 years. Terminology and criteria standard for clinical trials conducted by NIH were used.	0.43% 1/233 • Number of events 1 • During the 2-6 month pre-randomization run-in period and during follow-up from 2-6.5 years. Terminology and criteria standard for clinical trials conducted by NIH were used.	0.85% 2/234 • Number of events 2 • During the 2-6 month pre-randomization run-in period and during follow-up from 2-6.5 years. Terminology and criteria standard for clinical trials conducted by NIH were used.
Endocrine disorders Lactic acidosis	0.43% 1/232 • Number of events 1 • During the 2-6 month pre-randomization run-in period and during follow-up from 2-6.5 years. Terminology and criteria standard for clinical trials conducted by NIH were used.	0.00% 0/233 • During the 2-6 month pre-randomization run-in period and during follow-up from 2-6.5 years. Terminology and criteria standard for clinical trials conducted by NIH were used.	0.00% 0/234 • During the 2-6 month pre-randomization run-in period and during follow-up from 2-6.5 years. Terminology and criteria standard for clinical trials conducted by NIH were used.
General disorders all other	13.8% 32/232 • Number of events 32 • During the 2-6 month pre-randomization run-in period and during follow-up from 2-6.5 years. Terminology and criteria standard for clinical trials conducted by NIH were used.	10.7% 25/233 • Number of events 25 • During the 2-6 month pre-randomization run-in period and during follow-up from 2-6.5 years. Terminology and criteria standard for clinical trials conducted by NIH were used.	21.8% 51/234 • Number of events 51 • During the 2-6 month pre-randomization run-in period and during follow-up from 2-6.5 years. Terminology and criteria standard for clinical trials conducted by NIH were used.

Other adverse events

Other adverse events
Measure	1 Metformin Alone n=232 participants at risk Metformin alone Metformin: capsule, 1000 mg bid	2 Metformin + Rosliglitazone n=233 participants at risk Metformin + Rosiglitazone Metformin: capsule, 1000 mg bid Rosiglitazone: capsule, 4 mg bid	3 Metformin + Lifestyle Program n=234 participants at risk Metformin + Lifestyle Program Metformin: capsule, 1000 mg bid Lifestyle Program: a lifestyle change (LC) phase of weekly sessions for months 1-6, followed by a bi-weekly lifestyle maintenance (LM) phase through months 7-12, and a continued contact (CC) phase from months 13 through the end of the study. The CC phase sessions are scheduled monthly for the initial 12 months (study months 13-24) and then quarterly or 4 times a year to the end of the study
Skin and subcutaneous tissue disorders Skin rash on physical examination	46.6% 108/232 • Number of events 108 • During the 2-6 month pre-randomization run-in period and during follow-up from 2-6.5 years. Terminology and criteria standard for clinical trials conducted by NIH were used.	43.3% 101/233 • Number of events 101 • During the 2-6 month pre-randomization run-in period and during follow-up from 2-6.5 years. Terminology and criteria standard for clinical trials conducted by NIH were used.	40.6% 95/234 • Number of events 95 • During the 2-6 month pre-randomization run-in period and during follow-up from 2-6.5 years. Terminology and criteria standard for clinical trials conducted by NIH were used.
Gastrointestinal disorders Gastrointestinal symptoms	55.6% 129/232 • Number of events 129 • During the 2-6 month pre-randomization run-in period and during follow-up from 2-6.5 years. Terminology and criteria standard for clinical trials conducted by NIH were used.	42.9% 100/233 • Number of events 100 • During the 2-6 month pre-randomization run-in period and during follow-up from 2-6.5 years. Terminology and criteria standard for clinical trials conducted by NIH were used.	58.1% 136/234 • Number of events 136 • During the 2-6 month pre-randomization run-in period and during follow-up from 2-6.5 years. Terminology and criteria standard for clinical trials conducted by NIH were used.
Skin and subcutaneous tissue disorders Edema on physical examination	7.3% 17/232 • Number of events 17 • During the 2-6 month pre-randomization run-in period and during follow-up from 2-6.5 years. Terminology and criteria standard for clinical trials conducted by NIH were used.	7.3% 17/233 • Number of events 17 • During the 2-6 month pre-randomization run-in period and during follow-up from 2-6.5 years. Terminology and criteria standard for clinical trials conducted by NIH were used.	7.3% 17/234 • Number of events 17 • During the 2-6 month pre-randomization run-in period and during follow-up from 2-6.5 years. Terminology and criteria standard for clinical trials conducted by NIH were used.
Endocrine disorders Hyperglycemia symptoms	49.6% 115/232 • Number of events 115 • During the 2-6 month pre-randomization run-in period and during follow-up from 2-6.5 years. Terminology and criteria standard for clinical trials conducted by NIH were used.	42.1% 98/233 • Number of events 98 • During the 2-6 month pre-randomization run-in period and during follow-up from 2-6.5 years. Terminology and criteria standard for clinical trials conducted by NIH were used.	44.0% 103/234 • Number of events 103 • During the 2-6 month pre-randomization run-in period and during follow-up from 2-6.5 years. Terminology and criteria standard for clinical trials conducted by NIH were used.
Infections and infestations Infection requiring medical attention	64.2% 149/232 • Number of events 149 • During the 2-6 month pre-randomization run-in period and during follow-up from 2-6.5 years. Terminology and criteria standard for clinical trials conducted by NIH were used.	51.5% 120/233 • Number of events 120 • During the 2-6 month pre-randomization run-in period and during follow-up from 2-6.5 years. Terminology and criteria standard for clinical trials conducted by NIH were used.	64.5% 151/234 • Number of events 151 • During the 2-6 month pre-randomization run-in period and during follow-up from 2-6.5 years. Terminology and criteria standard for clinical trials conducted by NIH were used.
Musculoskeletal and connective tissue disorders Sprain or fracture requiring medical attention	28.4% 66/232 • Number of events 66 • During the 2-6 month pre-randomization run-in period and during follow-up from 2-6.5 years. Terminology and criteria standard for clinical trials conducted by NIH were used.	22.7% 53/233 • Number of events 53 • During the 2-6 month pre-randomization run-in period and during follow-up from 2-6.5 years. Terminology and criteria standard for clinical trials conducted by NIH were used.	27.4% 64/234 • Number of events 64 • During the 2-6 month pre-randomization run-in period and during follow-up from 2-6.5 years. Terminology and criteria standard for clinical trials conducted by NIH were used.
Musculoskeletal and connective tissue disorders Muscle ache or pain	29.3% 68/232 • Number of events 68 • During the 2-6 month pre-randomization run-in period and during follow-up from 2-6.5 years. Terminology and criteria standard for clinical trials conducted by NIH were used.	22.7% 53/233 • Number of events 53 • During the 2-6 month pre-randomization run-in period and during follow-up from 2-6.5 years. Terminology and criteria standard for clinical trials conducted by NIH were used.	32.9% 77/234 • Number of events 77 • During the 2-6 month pre-randomization run-in period and during follow-up from 2-6.5 years. Terminology and criteria standard for clinical trials conducted by NIH were used.
Endocrine disorders Mild hypoglycemia	4.3% 10/232 • Number of events 10 • During the 2-6 month pre-randomization run-in period and during follow-up from 2-6.5 years. Terminology and criteria standard for clinical trials conducted by NIH were used.	8.2% 19/233 • Number of events 19 • During the 2-6 month pre-randomization run-in period and during follow-up from 2-6.5 years. Terminology and criteria standard for clinical trials conducted by NIH were used.	3.4% 8/234 • Number of events 8 • During the 2-6 month pre-randomization run-in period and during follow-up from 2-6.5 years. Terminology and criteria standard for clinical trials conducted by NIH were used.

Additional Information

Dr. Kathryn Hirst, Coordinating Center PI

TODAY Coordinating Center at George Washington University Biostatistics Center

Phone: 301-881-9260

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee This work was conducted by a collaborative group. All investigators in the study group adhere to the Publications \& Presentations Policy. The policy spells out procedures for proposing, developing, and submitting publications and presentations using study data. Once results have been published or presented, all members of the study group are free to discuss them.
Publication restrictions are in place

Restriction type: OTHER