Trial Outcomes & Findings for The Health Influences of Puberty (HIP) Study (NCT NCT01775813)
NCT ID: NCT01775813
Last Updated: 2022-02-01
Results Overview
As measured by in intravenous glucose tolerance test (IVGTT) as calculated by Bergman's minimal model. Higher numbers indicate a better outcome. Patients are randomized to receive metformin or placebo at Tanner stage 2-3 of puberty. They are reassessed at Tanner 4 and again at Tanner 5. At that point, the treatment is stopped and they are reassessed 6 months after stopping treatment to see if effects of treatment persist.
Recruitment status
COMPLETED
Study phase
PHASE4
Target enrollment
104 participants
Primary outcome timeframe
Baseline, Tanner (puberty) stage 4-average 1.5 years from baseline, Tanner (puberty) stage 5-average 2.5 yrs from baseline, 6 mos post-treatment-average 3 yrs from baseline
Results posted on
2022-02-01
Participant Flow
Participant milestones
| Measure |
Normal Weight
Normal Weight by BMI. No treatment.
|
Obese - NT
Obese by BMI. These participants were not prescribed any intervention (Non-treated).
|
Obese - Placebo
Dosage form: Stamped placebo pill to look like the 1000 mg metformin pill Dosage: 1 pill taken orally twice daily Duration: From early puberty (Tanner 3-4) until puberty completion (Tanner 5), approximately 3 years
|
Obese - Metformin
Dosage form: Metformin 1000 mg tablets Dosage: 1000 mg by mouth twice daily Duration: From early puberty (Tanner 3-4) until puberty completion (Tanner 5), approximately 3 years
|
|---|---|---|---|---|
|
Overall Study
STARTED
|
47
|
13
|
24
|
20
|
|
Overall Study
Study Visit 2 (Tanner 4)
|
36
|
4
|
11
|
11
|
|
Overall Study
Study Visit 3 (Tanner 5)
|
34
|
8
|
12
|
11
|
|
Overall Study
Study Visit 4 (Post-Puberty)
|
10
|
0
|
13
|
11
|
|
Overall Study
COMPLETED
|
34
|
8
|
12
|
11
|
|
Overall Study
NOT COMPLETED
|
13
|
5
|
12
|
9
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
The Health Influences of Puberty (HIP) Study
Baseline characteristics by cohort
| Measure |
Normal Weight
n=47 Participants
Normal Weight by BMI. No treatment.
|
Obese - NT
n=13 Participants
Obese by BMI. Participants were not taking metformin or placebo
|
Obese - Placebo
n=24 Participants
Dosage form: Stamped placebo pill to look like the 1000 mg metformin pill Dosage: 1 pill taken orally twice daily Duration: From early puberty (Tanner 3-4) until puberty completion (Tanner 5), approximately 3 years
|
Obese - Metformin
n=20 Participants
Dosage form: Metformin 1000 mg tablets Dosage: 1000 mg by mouth twice daily Duration: From early puberty (Tanner 3-4) until puberty completion (Tanner 5), approximately 3 years
|
Total
n=104 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|
|
Age, Continuous
|
12.070 years
STANDARD_DEVIATION 1.513 • n=99 Participants
|
11.274 years
STANDARD_DEVIATION 1.138 • n=107 Participants
|
11.146 years
STANDARD_DEVIATION 1.088 • n=206 Participants
|
11.863 years
STANDARD_DEVIATION 1.562 • n=7 Participants
|
11.754 years
STANDARD_DEVIATION 1.437 • n=31 Participants
|
|
Sex: Female, Male
Female
|
22 Participants
n=99 Participants
|
6 Participants
n=107 Participants
|
17 Participants
n=206 Participants
|
9 Participants
n=7 Participants
|
54 Participants
n=31 Participants
|
|
Sex: Female, Male
Male
|
25 Participants
n=99 Participants
|
7 Participants
n=107 Participants
|
7 Participants
n=206 Participants
|
11 Participants
n=7 Participants
|
50 Participants
n=31 Participants
|
|
Race/Ethnicity, Customized
Hispanic
|
12 Participants
n=99 Participants
|
7 Participants
n=107 Participants
|
19 Participants
n=206 Participants
|
16 Participants
n=7 Participants
|
54 Participants
n=31 Participants
|
|
Race/Ethnicity, Customized
Non-Hispanic White
|
23 Participants
n=99 Participants
|
4 Participants
n=107 Participants
|
2 Participants
n=206 Participants
|
1 Participants
n=7 Participants
|
30 Participants
n=31 Participants
|
|
Race/Ethnicity, Customized
Black
|
8 Participants
n=99 Participants
|
1 Participants
n=107 Participants
|
2 Participants
n=206 Participants
|
2 Participants
n=7 Participants
|
13 Participants
n=31 Participants
|
|
Race/Ethnicity, Customized
Asian
|
3 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
0 Participants
n=7 Participants
|
3 Participants
n=31 Participants
|
|
Race/Ethnicity, Customized
Other
|
1 Participants
n=99 Participants
|
1 Participants
n=107 Participants
|
1 Participants
n=206 Participants
|
0 Participants
n=7 Participants
|
3 Participants
n=31 Participants
|
|
Race/Ethnicity, Customized
Native American
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=31 Participants
|
|
Region of Enrollment
United States
|
47 participants
n=99 Participants
|
13 participants
n=107 Participants
|
24 participants
n=206 Participants
|
20 participants
n=7 Participants
|
104 participants
n=31 Participants
|
PRIMARY outcome
Timeframe: Baseline, Tanner (puberty) stage 4-average 1.5 years from baseline, Tanner (puberty) stage 5-average 2.5 yrs from baseline, 6 mos post-treatment-average 3 yrs from baselinePopulation: 24 participants analyzed in the Obese NT Placebo group are also analyzed in the Obese Placebo group.
As measured by in intravenous glucose tolerance test (IVGTT) as calculated by Bergman's minimal model. Higher numbers indicate a better outcome. Patients are randomized to receive metformin or placebo at Tanner stage 2-3 of puberty. They are reassessed at Tanner 4 and again at Tanner 5. At that point, the treatment is stopped and they are reassessed 6 months after stopping treatment to see if effects of treatment persist.
Outcome measures
| Measure |
Normal Weight
n=47 Participants
Normal Weight by BMI. No treatment.
|
Obese - NT
n=37 Participants
Obese by BMI. These participants were not assigned an intervention (non-treated).
|
Obese - Placebo
n=24 Participants
Dosage form: Stamped placebo pill to look like the 1000 mg metformin pill Dosage: 1 pill taken orally twice daily Duration: From early puberty (Tanner 3-4) until puberty completion (Tanner 5), approximately 3 years
|
Obese - Metformin
n=20 Participants
Dosage form: Metformin 1000 mg tablets Dosage: 1000 mg by mouth twice daily Duration: From early puberty (Tanner 3-4) until puberty completion (Tanner 5), approximately 3 years
|
|---|---|---|---|---|
|
Insulin Sensitivity
Tanner 4
|
6.661 x10-4/min-1/mIU/mL
Standard Deviation 4.418
|
1.995 x10-4/min-1/mIU/mL
Standard Deviation 0.959
|
1.868 x10-4/min-1/mIU/mL
Standard Deviation 1.102
|
2.873 x10-4/min-1/mIU/mL
Standard Deviation 2.155
|
|
Insulin Sensitivity
Baseline
|
8.559 x10-4/min-1/mIU/mL
Standard Deviation 5.755
|
3.425 x10-4/min-1/mIU/mL
Standard Deviation 4.197
|
3.756 x10-4/min-1/mIU/mL
Standard Deviation 4.970
|
2.985 x10-4/min-1/mIU/mL
Standard Deviation 2.656
|
|
Insulin Sensitivity
Tanner 5
|
6.438 x10-4/min-1/mIU/mL
Standard Deviation 3.835
|
2.082 x10-4/min-1/mIU/mL
Standard Deviation 1.764
|
2.383 x10-4/min-1/mIU/mL
Standard Deviation 2.056
|
2.990 x10-4/min-1/mIU/mL
Standard Deviation 3.038
|
|
Insulin Sensitivity
Post-Puberty
|
NA x10-4/min-1/mIU/mL
Standard Deviation NA
Not Measured
|
NA x10-4/min-1/mIU/mL
Standard Deviation NA
Not Measured
|
3.017 x10-4/min-1/mIU/mL
Standard Deviation 3.449
|
2.182 x10-4/min-1/mIU/mL
Standard Deviation 2.353
|
SECONDARY outcome
Timeframe: Baseline, Tanner (puberty) stage 4-average 1.5 years from baseline, Tanner (puberty) stage 5-average 2.5 yrs from baseline, 6 mos post-treatment-average 3 yrs from baselinePopulation: 24 participants analyzed in the Obese NT Placebo group are also analyzed in the Obese Placebo group.
As measured by IVGTT as calculated by Bergman's minimal model. Higher numbers indicate a better outcome. Please see primary outcome for more detail about timing of measurement.
Outcome measures
| Measure |
Normal Weight
n=47 Participants
Normal Weight by BMI. No treatment.
|
Obese - NT
n=37 Participants
Obese by BMI. These participants were not assigned an intervention (non-treated).
|
Obese - Placebo
n=24 Participants
Dosage form: Stamped placebo pill to look like the 1000 mg metformin pill Dosage: 1 pill taken orally twice daily Duration: From early puberty (Tanner 3-4) until puberty completion (Tanner 5), approximately 3 years
|
Obese - Metformin
n=20 Participants
Dosage form: Metformin 1000 mg tablets Dosage: 1000 mg by mouth twice daily Duration: From early puberty (Tanner 3-4) until puberty completion (Tanner 5), approximately 3 years
|
|---|---|---|---|---|
|
Insulin Secretion (Acute Insulin Response to Glucose, AIRg)
Tanner 4
|
783.191 µIU/mL
Standard Deviation 623.946
|
1951.323 µIU/mL
Standard Deviation 1035.697
|
1996.867 µIU/mL
Standard Deviation 1215.017
|
2157.349 µIU/mL
Standard Deviation 1099.876
|
|
Insulin Secretion (Acute Insulin Response to Glucose, AIRg)
Tanner 5
|
680.858 µIU/mL
Standard Deviation 572.884
|
2103.309 µIU/mL
Standard Deviation 1505.040
|
2013.628 µIU/mL
Standard Deviation 1417.407
|
1804.026 µIU/mL
Standard Deviation 761.849
|
|
Insulin Secretion (Acute Insulin Response to Glucose, AIRg)
Baseline
|
583.535 µIU/mL
Standard Deviation 432.753
|
1877.895 µIU/mL
Standard Deviation 1052.328
|
1858.16 µIU/mL
Standard Deviation 1079.128
|
2368.931 µIU/mL
Standard Deviation 1616.348
|
|
Insulin Secretion (Acute Insulin Response to Glucose, AIRg)
Post-Puberty
|
NA µIU/mL
Standard Deviation NA
Not Measured
|
NA µIU/mL
Standard Deviation NA
Not Measured
|
1943.542 µIU/mL
Standard Deviation 1353.036
|
1667.713 µIU/mL
Standard Deviation 917.270
|
SECONDARY outcome
Timeframe: Baseline, Tanner (puberty) stage 4-average 1.5 years from baseline, Tanner (puberty) stage 5-average 2.5 yrs from baseline, 6 mos post-treatment-average 3 yrs from baselinePopulation: 24 participants analyzed in the Obese NT Placebo group are also analyzed in the Obese Placebo group.
Please see primary outcome for more detail about timing of measurement. Disposition index is measured via (IVGTT) as calculated by Bergman's minimal model. Higher numbers indicate a better outcome. It reflects the product of outcome measures 1 and 2 (Si x AIRg).
Outcome measures
| Measure |
Normal Weight
n=47 Participants
Normal Weight by BMI. No treatment.
|
Obese - NT
n=37 Participants
Obese by BMI. These participants were not assigned an intervention (non-treated).
|
Obese - Placebo
n=24 Participants
Dosage form: Stamped placebo pill to look like the 1000 mg metformin pill Dosage: 1 pill taken orally twice daily Duration: From early puberty (Tanner 3-4) until puberty completion (Tanner 5), approximately 3 years
|
Obese - Metformin
n=20 Participants
Dosage form: Metformin 1000 mg tablets Dosage: 1000 mg by mouth twice daily Duration: From early puberty (Tanner 3-4) until puberty completion (Tanner 5), approximately 3 years
|
|---|---|---|---|---|
|
Disposition Index
Baseline
|
3750.463 x10-4/min-1
Standard Deviation 1625.015
|
4195.921 x10-4/min-1
Standard Deviation 1743.345
|
4286.209 x10-4/min-1
Standard Deviation 1966.920
|
4438.821 x10-4/min-1
Standard Deviation 2420.123
|
|
Disposition Index
Tanner 4
|
3706.940 x10-4/min-1
Standard Deviation 1972.563
|
3269.039 x10-4/min-1
Standard Deviation 1500.261
|
2897.689 x10-4/min-1
Standard Deviation 1553.948
|
5046.218 x10-4/min-1
Standard Deviation 2858.784
|
|
Disposition Index
Tanner 5
|
3234.061 x10-4/min-1
Standard Deviation 2474.754
|
2897.244 x10-4/min-1
Standard Deviation 1547.515
|
3194.773 x10-4/min-1
Standard Deviation 1918.812
|
3537.273 x10-4/min-1
Standard Deviation 768.858
|
|
Disposition Index
Post-Puberty
|
NA x10-4/min-1
Standard Deviation NA
Not Measured
|
NA x10-4/min-1
Standard Deviation NA
Not Measured
|
3627.762 x10-4/min-1
Standard Deviation 2375.166
|
2539.933 x10-4/min-1
Standard Deviation 1393.267
|
SECONDARY outcome
Timeframe: Baseline, Tanner (puberty) stage 4-average 1.5 years from baseline, Tanner (puberty) stage 5-average 2.5 yrs from baseline, 6 mos post-treatment-average 3 yrs from baselinePopulation: 24 participants analyzed in the Obese NT Placebo group are also analyzed in the Obese Placebo group.
Please see primary outcome for more detail about timing of measurement.
Outcome measures
| Measure |
Normal Weight
n=47 Participants
Normal Weight by BMI. No treatment.
|
Obese - NT
n=37 Participants
Obese by BMI. These participants were not assigned an intervention (non-treated).
|
Obese - Placebo
n=24 Participants
Dosage form: Stamped placebo pill to look like the 1000 mg metformin pill Dosage: 1 pill taken orally twice daily Duration: From early puberty (Tanner 3-4) until puberty completion (Tanner 5), approximately 3 years
|
Obese - Metformin
n=20 Participants
Dosage form: Metformin 1000 mg tablets Dosage: 1000 mg by mouth twice daily Duration: From early puberty (Tanner 3-4) until puberty completion (Tanner 5), approximately 3 years
|
|---|---|---|---|---|
|
Low Density Lipoprotein
Baseline
|
79.488 mg/dl
Standard Deviation 22.691
|
86.533 mg/dl
Standard Deviation 22.543
|
88.583 mg/dl
Standard Deviation 23.824
|
83.779 mg/dl
Standard Deviation 25.029
|
|
Low Density Lipoprotein
Tanner 4
|
75.367 mg/dl
Standard Deviation 15.852
|
96.636 mg/dl
Standard Deviation 19.464
|
96.636 mg/dl
Standard Deviation 19.464
|
81.818 mg/dl
Standard Deviation 24.677
|
|
Low Density Lipoprotein
Tanner 5
|
78.485 mg/dl
Standard Deviation 20.520
|
96.222 mg/dl
Standard Deviation 24.422
|
97.667 mg/dl
Standard Deviation 27.655
|
75.000 mg/dl
Standard Deviation 27.799
|
|
Low Density Lipoprotein
Post-Puberty
|
NA mg/dl
Standard Deviation NA
Not Measured
|
NA mg/dl
Standard Deviation NA
Not Measured
|
103.154 mg/dl
Standard Deviation 26.620
|
86.545 mg/dl
Standard Deviation 28.507
|
SECONDARY outcome
Timeframe: Baseline, Tanner (puberty) stage 4-average 1.5 years from baseline, Tanner (puberty) stage 5-average 2.5 yrs from baselinePopulation: 24 participants analyzed in the Obese NT Placebo group are also analyzed in the Obese Placebo group.
IGF-1 measured in serum at each time point
Outcome measures
| Measure |
Normal Weight
n=47 Participants
Normal Weight by BMI. No treatment.
|
Obese - NT
n=37 Participants
Obese by BMI. These participants were not assigned an intervention (non-treated).
|
Obese - Placebo
n=24 Participants
Dosage form: Stamped placebo pill to look like the 1000 mg metformin pill Dosage: 1 pill taken orally twice daily Duration: From early puberty (Tanner 3-4) until puberty completion (Tanner 5), approximately 3 years
|
Obese - Metformin
n=20 Participants
Dosage form: Metformin 1000 mg tablets Dosage: 1000 mg by mouth twice daily Duration: From early puberty (Tanner 3-4) until puberty completion (Tanner 5), approximately 3 years
|
|---|---|---|---|---|
|
Insulin-like Growth Factor 1
Baseline
|
313.500 ng/ml
Standard Deviation 103.339
|
262.278 ng/ml
Standard Deviation 91.924
|
243.042 ng/ml
Standard Deviation 85.040
|
281.700 ng/ml
Standard Deviation 86.014
|
|
Insulin-like Growth Factor 1
Tanner 4
|
405.389 ng/ml
Standard Deviation 116.845
|
370.800 ng/ml
Standard Deviation 89.816
|
380.273 ng/ml
Standard Deviation 77.040
|
410.300 ng/ml
Standard Deviation 116.467
|
|
Insulin-like Growth Factor 1
Tanner 5
|
398.000 ng/ml
Standard Deviation 97.117
|
389.800 ng/ml
Standard Deviation 116.087
|
351.833 ng/ml
Standard Deviation 74.909
|
404.800 ng/ml
Standard Deviation 88.745
|
|
Insulin-like Growth Factor 1
Post-Puberty
|
NA ng/ml
Standard Deviation NA
Not Measured
|
NA ng/ml
Standard Deviation NA
Not Measured
|
319.692 ng/ml
Standard Deviation 93.694
|
395.818 ng/ml
Standard Deviation 114.417
|
SECONDARY outcome
Timeframe: Baseline, Tanner (puberty) stage 4-average 1.5 years from baseline, Tanner (puberty) stage 5-average 2.5 yrs from baselinePopulation: 24 participants analyzed in the Obese NT Placebo group are also analyzed in the Obese Placebo group.
Testosterone measured in serum at each time point
Outcome measures
| Measure |
Normal Weight
n=47 Participants
Normal Weight by BMI. No treatment.
|
Obese - NT
n=37 Participants
Obese by BMI. These participants were not assigned an intervention (non-treated).
|
Obese - Placebo
n=24 Participants
Dosage form: Stamped placebo pill to look like the 1000 mg metformin pill Dosage: 1 pill taken orally twice daily Duration: From early puberty (Tanner 3-4) until puberty completion (Tanner 5), approximately 3 years
|
Obese - Metformin
n=20 Participants
Dosage form: Metformin 1000 mg tablets Dosage: 1000 mg by mouth twice daily Duration: From early puberty (Tanner 3-4) until puberty completion (Tanner 5), approximately 3 years
|
|---|---|---|---|---|
|
Total Testosterone
Baseline
|
108.625 ng/dl
Standard Deviation 135.377
|
35.278 ng/dl
Standard Deviation 28.375
|
30.125 ng/dl
Standard Deviation 20.422
|
41.050 ng/dl
Standard Deviation 32.705
|
|
Total Testosterone
Tanner 4
|
145.972 ng/dl
Standard Deviation 159.866
|
87.933 ng/dl
Standard Deviation 103.902
|
89.364 ng/dl
Standard Deviation 105.331
|
121.727 ng/dl
Standard Deviation 113.418
|
|
Total Testosterone
Tanner 5
|
235.559 ng/dl
Standard Deviation 235.224
|
158.300 ng/dl
Standard Deviation 234.056
|
165.750 ng/dl
Standard Deviation 282.171
|
117.909 ng/dl
Standard Deviation 132.301
|
|
Total Testosterone
Post-Puberty
|
NA ng/dl
Standard Deviation NA
Not Measured
|
NA ng/dl
Standard Deviation NA
Not Measured
|
152.692 ng/dl
Standard Deviation 168.109
|
150.727 ng/dl
Standard Deviation 161.357
|
SECONDARY outcome
Timeframe: Baseline, Tanner (puberty) stage 4-average 1.5 years from baseline, Tanner (puberty) stage 5-average 2.5 yrs from baselinePopulation: 24 participants analyzed in the Obese NT Placebo group are also analyzed in the Obese Placebo group.
Estradiol measured in serum at each time point
Outcome measures
| Measure |
Normal Weight
n=47 Participants
Normal Weight by BMI. No treatment.
|
Obese - NT
n=37 Participants
Obese by BMI. These participants were not assigned an intervention (non-treated).
|
Obese - Placebo
n=24 Participants
Dosage form: Stamped placebo pill to look like the 1000 mg metformin pill Dosage: 1 pill taken orally twice daily Duration: From early puberty (Tanner 3-4) until puberty completion (Tanner 5), approximately 3 years
|
Obese - Metformin
n=20 Participants
Dosage form: Metformin 1000 mg tablets Dosage: 1000 mg by mouth twice daily Duration: From early puberty (Tanner 3-4) until puberty completion (Tanner 5), approximately 3 years
|
|---|---|---|---|---|
|
Estradiol
Baseline
|
22.375 pg/mL
Standard Deviation 34.068
|
15.722 pg/mL
Standard Deviation 7.756
|
15.833 pg/mL
Standard Deviation 7.738
|
14.750 pg/mL
Standard Deviation 6.695
|
|
Estradiol
Tanner 4
|
50.583 pg/mL
Standard Deviation 70.888
|
35.867 pg/mL
Standard Deviation 49.693
|
44.545 pg/mL
Standard Deviation 56.077
|
23.364 pg/mL
Standard Deviation 14.123
|
|
Estradiol
Tanner 5
|
57.382 pg/mL
Standard Deviation 79.251
|
42.800 pg/mL
Standard Deviation 38.324
|
48.833 pg/mL
Standard Deviation 47.610
|
48.000 pg/mL
Standard Deviation 29.192
|
|
Estradiol
Post-Puberty
|
NA pg/mL
Standard Deviation NA
Not Measured
|
NA pg/mL
Standard Deviation NA
Not Measured
|
70.923 pg/mL
Standard Deviation 91.316
|
69.636 pg/mL
Standard Deviation 85.940
|
SECONDARY outcome
Timeframe: Baseline, Tanner (puberty) stage 4-average 1.5 years from baseline, Tanner (puberty) stage 5-average 2.5 yrs from baselinePopulation: 24 participants analyzed in the Obese NT Placebo group are also analyzed in the Obese Placebo group.
SHBG measured in serum at each time point
Outcome measures
| Measure |
Normal Weight
n=47 Participants
Normal Weight by BMI. No treatment.
|
Obese - NT
n=37 Participants
Obese by BMI. These participants were not assigned an intervention (non-treated).
|
Obese - Placebo
n=24 Participants
Dosage form: Stamped placebo pill to look like the 1000 mg metformin pill Dosage: 1 pill taken orally twice daily Duration: From early puberty (Tanner 3-4) until puberty completion (Tanner 5), approximately 3 years
|
Obese - Metformin
n=20 Participants
Dosage form: Metformin 1000 mg tablets Dosage: 1000 mg by mouth twice daily Duration: From early puberty (Tanner 3-4) until puberty completion (Tanner 5), approximately 3 years
|
|---|---|---|---|---|
|
Sex Hormone Binding Globulin
Baseline
|
61.958 nmol/l
Standard Deviation 21.680
|
20.417 nmol/l
Standard Deviation 8.310
|
18.958 nmol/l
Standard Deviation 6.805
|
17.550 nmol/l
Standard Deviation 8.451
|
|
Sex Hormone Binding Globulin
Tanner 4
|
50.417 nmol/l
Standard Deviation 24.098
|
17.200 nmol/l
Standard Deviation 7.580
|
16.364 nmol/l
Standard Deviation 6.742
|
19.545 nmol/l
Standard Deviation 14.348
|
|
Sex Hormone Binding Globulin
Tanner 5
|
43.500 nmol/l
Standard Deviation 15.498
|
16.250 nmol/l
Standard Deviation 5.581
|
15.750 nmol/l
Standard Deviation 6.468
|
16.455 nmol/l
Standard Deviation 8.825
|
|
Sex Hormone Binding Globulin
Post-Puberty
|
NA nmol/l
Standard Deviation NA
Not Measured
|
NA nmol/l
Standard Deviation NA
Not Measured
|
15.538 nmol/l
Standard Deviation 4.409
|
17.273 nmol/l
Standard Deviation 10.640
|
SECONDARY outcome
Timeframe: Baseline, Tanner (puberty) stage 4-average 1.5 years from baseline, Tanner (puberty) stage 5-average 2.5 yrs from baselineDHEA-S measured in serum at each time point
Outcome measures
| Measure |
Normal Weight
n=47 Participants
Normal Weight by BMI. No treatment.
|
Obese - NT
n=37 Participants
Obese by BMI. These participants were not assigned an intervention (non-treated).
|
Obese - Placebo
n=24 Participants
Dosage form: Stamped placebo pill to look like the 1000 mg metformin pill Dosage: 1 pill taken orally twice daily Duration: From early puberty (Tanner 3-4) until puberty completion (Tanner 5), approximately 3 years
|
Obese - Metformin
n=20 Participants
Dosage form: Metformin 1000 mg tablets Dosage: 1000 mg by mouth twice daily Duration: From early puberty (Tanner 3-4) until puberty completion (Tanner 5), approximately 3 years
|
|---|---|---|---|---|
|
Dehydroepiandrosterone Sulfate
Baseline
|
90.146 mcg/dl
Standard Deviation 60.522
|
96.750 mcg/dl
Standard Deviation 63.592
|
91.167 mcg/dl
Standard Deviation 60.501
|
107.600 mcg/dl
Standard Deviation 64.722
|
|
Dehydroepiandrosterone Sulfate
Tanner 4
|
101.889 mcg/dl
Standard Deviation 62.016
|
101.533 mcg/dl
Standard Deviation 67.038
|
116.182 mcg/dl
Standard Deviation 71.822
|
129.545 mcg/dl
Standard Deviation 69.398
|
|
Dehydroepiandrosterone Sulfate
Tanner 5
|
130.206 mcg/dl
Standard Deviation 69.229
|
137.250 mcg/dl
Standard Deviation 74.248
|
137.083 mcg/dl
Standard Deviation 86.885
|
145.818 mcg/dl
Standard Deviation 66.535
|
|
Dehydroepiandrosterone Sulfate
Post-Puberty
|
NA mcg/dl
Standard Deviation NA
Not Measured
|
NA mcg/dl
Standard Deviation NA
Not Measured
|
132.154 mcg/dl
Standard Deviation 68.295
|
176.818 mcg/dl
Standard Deviation 110.840
|
SECONDARY outcome
Timeframe: Baseline, Tanner (puberty) stage 4-average 1.5 years from baseline, Tanner (puberty) stage 5-average 2.5 yrs from baselinePopulation: 24 participants analyzed in the Obese NT Placebo group are also analyzed in the Obese Placebo group.
hsCRP measured in serum at each time point
Outcome measures
| Measure |
Normal Weight
n=47 Participants
Normal Weight by BMI. No treatment.
|
Obese - NT
n=37 Participants
Obese by BMI. These participants were not assigned an intervention (non-treated).
|
Obese - Placebo
n=24 Participants
Dosage form: Stamped placebo pill to look like the 1000 mg metformin pill Dosage: 1 pill taken orally twice daily Duration: From early puberty (Tanner 3-4) until puberty completion (Tanner 5), approximately 3 years
|
Obese - Metformin
n=20 Participants
Dosage form: Metformin 1000 mg tablets Dosage: 1000 mg by mouth twice daily Duration: From early puberty (Tanner 3-4) until puberty completion (Tanner 5), approximately 3 years
|
|---|---|---|---|---|
|
High Sensitivity C-reactive Protein
Baseline
|
1.001 units on a scale
Standard Deviation 2.604
|
2.523 units on a scale
Standard Deviation 2.644
|
3.117 units on a scale
Standard Deviation 3.060
|
3.962 units on a scale
Standard Deviation 3.608
|
|
High Sensitivity C-reactive Protein
Tanner 4
|
0.305 units on a scale
Standard Deviation 0.631
|
4.530 units on a scale
Standard Deviation 5.034
|
4.357 units on a scale
Standard Deviation 5.661
|
1.841 units on a scale
Standard Deviation 1.494
|
|
High Sensitivity C-reactive Protein
Tanner 5
|
1.015 units on a scale
Standard Deviation 3.265
|
3.331 units on a scale
Standard Deviation 3.814
|
3.985 units on a scale
Standard Deviation 4.681
|
0.961 units on a scale
Standard Deviation 0.915
|
|
High Sensitivity C-reactive Protein
Post-Puberty
|
NA units on a scale
Standard Deviation NA
Not Measured
|
NA units on a scale
Standard Deviation NA
Not Measured
|
3.958 units on a scale
Standard Deviation 3.510
|
2.667 units on a scale
Standard Deviation 4.647
|
SECONDARY outcome
Timeframe: Baseline, Tanner (puberty) stage 4-average 1.5 years from baseline, Tanner (puberty) stage 5-average 2.5 yrs from baselinePopulation: 24 participants analyzed in the Obese NT Placebo group are also analyzed in the Obese Placebo group.
AST measured in serum at each time point
Outcome measures
| Measure |
Normal Weight
n=47 Participants
Normal Weight by BMI. No treatment.
|
Obese - NT
n=37 Participants
Obese by BMI. These participants were not assigned an intervention (non-treated).
|
Obese - Placebo
n=24 Participants
Dosage form: Stamped placebo pill to look like the 1000 mg metformin pill Dosage: 1 pill taken orally twice daily Duration: From early puberty (Tanner 3-4) until puberty completion (Tanner 5), approximately 3 years
|
Obese - Metformin
n=20 Participants
Dosage form: Metformin 1000 mg tablets Dosage: 1000 mg by mouth twice daily Duration: From early puberty (Tanner 3-4) until puberty completion (Tanner 5), approximately 3 years
|
|---|---|---|---|---|
|
Aspartate Aminotransferase (AST)
Baseline
|
42.174 international units per liter
Standard Deviation 14.685
|
41.250 international units per liter
Standard Deviation 18.130
|
43.542 international units per liter
Standard Deviation 20.156
|
54.150 international units per liter
Standard Deviation 28.117
|
|
Aspartate Aminotransferase (AST)
Tanner 4
|
35.706 international units per liter
Standard Deviation 11.202
|
44.429 international units per liter
Standard Deviation 25.621
|
43.636 international units per liter
Standard Deviation 26.070
|
40.273 international units per liter
Standard Deviation 14.065
|
|
Aspartate Aminotransferase (AST)
Tanner 5
|
33.364 international units per liter
Standard Deviation 11.811
|
36.650 international units per liter
Standard Deviation 17.458
|
42.333 international units per liter
Standard Deviation 20.331
|
34.091 international units per liter
Standard Deviation 11.122
|
|
Aspartate Aminotransferase (AST)
Post-Puberty
|
NA international units per liter
Standard Deviation NA
Not Measured
|
NA international units per liter
Standard Deviation NA
Not Measured
|
39.077 international units per liter
Standard Deviation 21.278
|
36.273 international units per liter
Standard Deviation 17.396
|
SECONDARY outcome
Timeframe: Baseline (Tanner 2-3), Tanner 4, Tanner 5Population: 24 participants analyzed in the Obese NT Placebo group are also analyzed in the Obese Placebo group.
ALT measured in serum at each time point
Outcome measures
| Measure |
Normal Weight
n=47 Participants
Normal Weight by BMI. No treatment.
|
Obese - NT
n=37 Participants
Obese by BMI. These participants were not assigned an intervention (non-treated).
|
Obese - Placebo
n=24 Participants
Dosage form: Stamped placebo pill to look like the 1000 mg metformin pill Dosage: 1 pill taken orally twice daily Duration: From early puberty (Tanner 3-4) until puberty completion (Tanner 5), approximately 3 years
|
Obese - Metformin
n=20 Participants
Dosage form: Metformin 1000 mg tablets Dosage: 1000 mg by mouth twice daily Duration: From early puberty (Tanner 3-4) until puberty completion (Tanner 5), approximately 3 years
|
|---|---|---|---|---|
|
Alanine Transaminase (ALT)
Baseline
|
25.022 international units per liter
Standard Deviation 9.556
|
35.194 international units per liter
Standard Deviation 22.132
|
41.125 international units per liter
Standard Deviation 24.552
|
52.400 international units per liter
Standard Deviation 50.296
|
|
Alanine Transaminase (ALT)
Tanner 4
|
27.059 international units per liter
Standard Deviation 7.671
|
44.571 international units per liter
Standard Deviation 40.839
|
51.182 international units per liter
Standard Deviation 43.829
|
42.545 international units per liter
Standard Deviation 18.753
|
|
Alanine Transaminase (ALT)
Tanner 5
|
26.121 international units per liter
Standard Deviation 6.859
|
38.650 international units per liter
Standard Deviation 23.089
|
47.500 international units per liter
Standard Deviation 25.995
|
39.636 international units per liter
Standard Deviation 17.328
|
|
Alanine Transaminase (ALT)
Post-Puberty
|
NA international units per liter
Standard Deviation NA
Not Measured
|
NA international units per liter
Standard Deviation NA
Not Measured
|
50.231 international units per liter
Standard Deviation 36.967
|
45.000 international units per liter
Standard Deviation 30.864
|
SECONDARY outcome
Timeframe: Baseline, every 6 months during the trial, Final visit (average 3 yrs after baseline)Population: 24 participants analyzed in the Obese NT Placebo group are also analyzed in the Obese Placebo group.
LH measured in an overnight urine sample at time points below
Outcome measures
| Measure |
Normal Weight
n=47 Participants
Normal Weight by BMI. No treatment.
|
Obese - NT
n=37 Participants
Obese by BMI. These participants were not assigned an intervention (non-treated).
|
Obese - Placebo
n=24 Participants
Dosage form: Stamped placebo pill to look like the 1000 mg metformin pill Dosage: 1 pill taken orally twice daily Duration: From early puberty (Tanner 3-4) until puberty completion (Tanner 5), approximately 3 years
|
Obese - Metformin
n=20 Participants
Dosage form: Metformin 1000 mg tablets Dosage: 1000 mg by mouth twice daily Duration: From early puberty (Tanner 3-4) until puberty completion (Tanner 5), approximately 3 years
|
|---|---|---|---|---|
|
Change in Urinary Luteinizing Hormone
Tanner 2/3
|
3.849 international units per liter
Standard Deviation 4.530
|
2.257 international units per liter
Standard Deviation 2.186
|
2.257 international units per liter
Standard Deviation 2.186
|
3.809 international units per liter
Standard Deviation 3.667
|
|
Change in Urinary Luteinizing Hormone
Tanner 4
|
4.518 international units per liter
Standard Deviation 8.496
|
3.310 international units per liter
Standard Deviation 3.793
|
3.310 international units per liter
Standard Deviation 3.793
|
3.729 international units per liter
Standard Deviation 4.036
|
|
Change in Urinary Luteinizing Hormone
Tanner 5
|
4.494 international units per liter
Standard Deviation 7.616
|
2.014 international units per liter
Standard Deviation 1.442
|
2.014 international units per liter
Standard Deviation 1.442
|
8.993 international units per liter
Standard Deviation 14.725
|
|
Change in Urinary Luteinizing Hormone
Post-Puberty
|
NA international units per liter
Standard Deviation NA
Not Measured
|
5.373 international units per liter
Standard Deviation 11.363
|
5.373 international units per liter
Standard Deviation 11.363
|
30.861 international units per liter
Standard Deviation 62.387
|
SECONDARY outcome
Timeframe: Baseline, every 6 months during the trial, Final visit-average 3 yrs after baselinePopulation: 24 participants analyzed in the Obese NT Placebo group are also analyzed in the Obese Placebo group.
FSH measured in overnight urine sample at time points below
Outcome measures
| Measure |
Normal Weight
n=47 Participants
Normal Weight by BMI. No treatment.
|
Obese - NT
n=37 Participants
Obese by BMI. These participants were not assigned an intervention (non-treated).
|
Obese - Placebo
n=24 Participants
Dosage form: Stamped placebo pill to look like the 1000 mg metformin pill Dosage: 1 pill taken orally twice daily Duration: From early puberty (Tanner 3-4) until puberty completion (Tanner 5), approximately 3 years
|
Obese - Metformin
n=20 Participants
Dosage form: Metformin 1000 mg tablets Dosage: 1000 mg by mouth twice daily Duration: From early puberty (Tanner 3-4) until puberty completion (Tanner 5), approximately 3 years
|
|---|---|---|---|---|
|
Change in Urinary Follicle-stimulating Hormone
Tanner 2/3
|
3.911 international units per milliliter (IU/m
Standard Deviation 5.590
|
3.837 international units per milliliter (IU/m
Standard Deviation 4.264
|
3.837 international units per milliliter (IU/m
Standard Deviation 4.264
|
3.615 international units per milliliter (IU/m
Standard Deviation 4.356
|
|
Change in Urinary Follicle-stimulating Hormone
Tanner 4
|
2.555 international units per milliliter (IU/m
Standard Deviation 2.541
|
4.874 international units per milliliter (IU/m
Standard Deviation 3.586
|
4.874 international units per milliliter (IU/m
Standard Deviation 3.586
|
3.162 international units per milliliter (IU/m
Standard Deviation 2.686
|
|
Change in Urinary Follicle-stimulating Hormone
Tanner 5
|
6.540 international units per milliliter (IU/m
Standard Deviation 9.360
|
4.093 international units per milliliter (IU/m
Standard Deviation 3.962
|
4.093 international units per milliliter (IU/m
Standard Deviation 3.962
|
3.213 international units per milliliter (IU/m
Standard Deviation 3.323
|
|
Change in Urinary Follicle-stimulating Hormone
Post-Puberty
|
NA international units per milliliter (IU/m
Standard Deviation NA
Not Measured
|
5.993 international units per milliliter (IU/m
Standard Deviation 6.429
|
5.993 international units per milliliter (IU/m
Standard Deviation 6.429
|
3.911 international units per milliliter (IU/m
Standard Deviation 2.689
|
SECONDARY outcome
Timeframe: Baseline, every 6 months during the trial, Final visit-average 3 yrs after baselinePopulation: 24 participants analyzed in the Obese NT Placebo group are also analyzed in the Obese Placebo group.
estradiol metabolite (E1c) measured in an overnight urine sample at each time point
Outcome measures
| Measure |
Normal Weight
n=47 Participants
Normal Weight by BMI. No treatment.
|
Obese - NT
n=37 Participants
Obese by BMI. These participants were not assigned an intervention (non-treated).
|
Obese - Placebo
n=24 Participants
Dosage form: Stamped placebo pill to look like the 1000 mg metformin pill Dosage: 1 pill taken orally twice daily Duration: From early puberty (Tanner 3-4) until puberty completion (Tanner 5), approximately 3 years
|
Obese - Metformin
n=20 Participants
Dosage form: Metformin 1000 mg tablets Dosage: 1000 mg by mouth twice daily Duration: From early puberty (Tanner 3-4) until puberty completion (Tanner 5), approximately 3 years
|
|---|---|---|---|---|
|
Change in Urinary Estradiol Metabolites
Tanner 2/3
|
7.711 ng/mgCr
Standard Deviation 22.531
|
17.353 ng/mgCr
Standard Deviation 17.214
|
17.353 ng/mgCr
Standard Deviation 17.214
|
28.451 ng/mgCr
Standard Deviation 26.082
|
|
Change in Urinary Estradiol Metabolites
Tanner 4
|
22.919 ng/mgCr
Standard Deviation 37.835
|
8.584 ng/mgCr
Standard Deviation 9.932
|
8.584 ng/mgCr
Standard Deviation 9.932
|
37.722 ng/mgCr
Standard Deviation 34.648
|
|
Change in Urinary Estradiol Metabolites
Tanner 5
|
41.036 ng/mgCr
Standard Deviation 78.160
|
7.825 ng/mgCr
Standard Deviation 2.586
|
7.825 ng/mgCr
Standard Deviation 2.586
|
71.546 ng/mgCr
Standard Deviation 77.343
|
|
Change in Urinary Estradiol Metabolites
Post-Puberty
|
NA ng/mgCr
Standard Deviation NA
Not Measured
|
26.402 ng/mgCr
Standard Deviation 38.299
|
26.402 ng/mgCr
Standard Deviation 38.299
|
30.883 ng/mgCr
Standard Deviation 33.674
|
SECONDARY outcome
Timeframe: Baseline, Tanner (puberty) stage 4-average 1.5 years from baseline, Tanner (puberty) stage 5-average 2.5 yrs from baselinePopulation: 24 participants analyzed in the Obese NT Placebo group are also analyzed in the Obese Placebo group.
HbA1c measured by HPLC at time points below
Outcome measures
| Measure |
Normal Weight
n=47 Participants
Normal Weight by BMI. No treatment.
|
Obese - NT
n=37 Participants
Obese by BMI. These participants were not assigned an intervention (non-treated).
|
Obese - Placebo
n=24 Participants
Dosage form: Stamped placebo pill to look like the 1000 mg metformin pill Dosage: 1 pill taken orally twice daily Duration: From early puberty (Tanner 3-4) until puberty completion (Tanner 5), approximately 3 years
|
Obese - Metformin
n=20 Participants
Dosage form: Metformin 1000 mg tablets Dosage: 1000 mg by mouth twice daily Duration: From early puberty (Tanner 3-4) until puberty completion (Tanner 5), approximately 3 years
|
|---|---|---|---|---|
|
Hemoglobin A1c
Baseline
|
5.139 mmol/mol
Standard Deviation 0.250
|
5.336 mmol/mol
Standard Deviation 0.488
|
5.336 mmol/mol
Standard Deviation 0.488
|
5.400 mmol/mol
Standard Deviation 0.286
|
|
Hemoglobin A1c
Tanner 4
|
5.200 mmol/mol
Standard Deviation 0.260
|
5.627 mmol/mol
Standard Deviation 0.531
|
5.627 mmol/mol
Standard Deviation 0.531
|
5.570 mmol/mol
Standard Deviation 0.250
|
|
Hemoglobin A1c
Tanner 5
|
5.233 mmol/mol
Standard Deviation 0.293
|
5.476 mmol/mol
Standard Deviation 0.360
|
5.500 mmol/mol
Standard Deviation 0.398
|
5.473 mmol/mol
Standard Deviation 0.552
|
|
Hemoglobin A1c
Post-Puberty
|
NA mmol/mol
Standard Deviation NA
Not Measured
|
NA mmol/mol
Standard Deviation NA
Not Measured
|
5.515 mmol/mol
Standard Deviation 0.519
|
5.691 mmol/mol
Standard Deviation 0.929
|
SECONDARY outcome
Timeframe: Baseline, Tanner (puberty) stage 4-average 1.5 years from baseline, Tanner (puberty) stage 5-average 2.5 yrs from baselinePopulation: 24 participants analyzed in the Obese NT Placebo group are also analyzed in the Obese Placebo group.
Leptin measured in serum at time points below
Outcome measures
| Measure |
Normal Weight
n=47 Participants
Normal Weight by BMI. No treatment.
|
Obese - NT
n=37 Participants
Obese by BMI. These participants were not assigned an intervention (non-treated).
|
Obese - Placebo
n=24 Participants
Dosage form: Stamped placebo pill to look like the 1000 mg metformin pill Dosage: 1 pill taken orally twice daily Duration: From early puberty (Tanner 3-4) until puberty completion (Tanner 5), approximately 3 years
|
Obese - Metformin
n=20 Participants
Dosage form: Metformin 1000 mg tablets Dosage: 1000 mg by mouth twice daily Duration: From early puberty (Tanner 3-4) until puberty completion (Tanner 5), approximately 3 years
|
|---|---|---|---|---|
|
Leptin
Baseline
|
5.956 ng/mL
Standard Deviation 5.616
|
32.097 ng/mL
Standard Deviation 13.624
|
33.917 ng/mL
Standard Deviation 15.207
|
32.215 ng/mL
Standard Deviation 17.027
|
|
Leptin
Tanner 4
|
5.964 ng/mL
Standard Deviation 4.582
|
36.867 ng/mL
Standard Deviation 20.519
|
44.036 ng/mL
Standard Deviation 19.121
|
29.791 ng/mL
Standard Deviation 21.892
|
|
Leptin
Tanner 5
|
8.338 ng/mL
Standard Deviation 7.088
|
38.155 ng/mL
Standard Deviation 21.061
|
47.642 ng/mL
Standard Deviation 21.269
|
31.182 ng/mL
Standard Deviation 20.982
|
|
Leptin
Post-Puberty
|
NA ng/mL
Standard Deviation NA
Not Measured
|
NA ng/mL
Standard Deviation NA
Not Measured
|
53.200 ng/mL
Standard Deviation 41.323
|
48.445 ng/mL
Standard Deviation 31.855
|
SECONDARY outcome
Timeframe: Baseline, Tanner (puberty) stage 4-average 1.5 years from baseline, Tanner (puberty) stage 5-average 2.5 yrs from baselinePopulation: 24 participants analyzed in the Obese NT Placebo group are also analyzed in the Obese Placebo group.
% body fat measured by DXA at time points below
Outcome measures
| Measure |
Normal Weight
n=47 Participants
Normal Weight by BMI. No treatment.
|
Obese - NT
n=37 Participants
Obese by BMI. These participants were not assigned an intervention (non-treated).
|
Obese - Placebo
n=24 Participants
Dosage form: Stamped placebo pill to look like the 1000 mg metformin pill Dosage: 1 pill taken orally twice daily Duration: From early puberty (Tanner 3-4) until puberty completion (Tanner 5), approximately 3 years
|
Obese - Metformin
n=20 Participants
Dosage form: Metformin 1000 mg tablets Dosage: 1000 mg by mouth twice daily Duration: From early puberty (Tanner 3-4) until puberty completion (Tanner 5), approximately 3 years
|
|---|---|---|---|---|
|
Percent Body Fat
Baseline
|
24.883 percentage of body fat
Standard Deviation 6.452
|
42.126 percentage of body fat
Standard Deviation 5.259
|
44.700 percentage of body fat
Standard Deviation 3.304
|
43.826 percentage of body fat
Standard Deviation 5.412
|
|
Percent Body Fat
Tanner 4
|
25.054 percentage of body fat
Standard Deviation 6.159
|
43.380 percentage of body fat
Standard Deviation 3.649
|
44.264 percentage of body fat
Standard Deviation 3.489
|
40.610 percentage of body fat
Standard Deviation 7.906
|
|
Percent Body Fat
Tanner 5
|
25.500 percentage of body fat
Standard Deviation 7.478
|
42.889 percentage of body fat
Standard Deviation 4.688
|
44.555 percentage of body fat
Standard Deviation 3.692
|
39.964 percentage of body fat
Standard Deviation 6.490
|
|
Percent Body Fat
Post-Puberty
|
NA percentage of body fat
Standard Deviation NA
Not Measured
|
NA percentage of body fat
Standard Deviation NA
Not Measured
|
43.962 percentage of body fat
Standard Deviation 5.701
|
41.418 percentage of body fat
Standard Deviation 5.669
|
SECONDARY outcome
Timeframe: Baseline, Tanner (puberty) stage 5-average 2.5 yrs from baselinePopulation: Data was not collected for some participants at all visits.
Percent Visceral Fat, Measured in a subset (10 per group) by single slice MRI
Outcome measures
| Measure |
Normal Weight
n=12 Participants
Normal Weight by BMI. No treatment.
|
Obese - NT
n=6 Participants
Obese by BMI. These participants were not assigned an intervention (non-treated).
|
Obese - Placebo
n=5 Participants
Dosage form: Stamped placebo pill to look like the 1000 mg metformin pill Dosage: 1 pill taken orally twice daily Duration: From early puberty (Tanner 3-4) until puberty completion (Tanner 5), approximately 3 years
|
Obese - Metformin
n=6 Participants
Dosage form: Metformin 1000 mg tablets Dosage: 1000 mg by mouth twice daily Duration: From early puberty (Tanner 3-4) until puberty completion (Tanner 5), approximately 3 years
|
|---|---|---|---|---|
|
Visceral Adipose
Baseline
|
7.647 Percent
Standard Deviation 3.702
|
12.007 Percent
Standard Deviation 2.263
|
12.076 Percent
Standard Deviation 3.968
|
12.007 Percent
Standard Deviation 2.263
|
|
Visceral Adipose
Tanner 5
|
6.322 Percent
Standard Deviation 2.676
|
12.236 Percent
Standard Deviation 1.564
|
10.079 Percent
Standard Deviation 1.886
|
12.236 Percent
Standard Deviation 1.564
|
SECONDARY outcome
Timeframe: Baseline, Tanner (puberty) stage 5-average 2.5 yrs from baselinePopulation: Data was not collected for some participants at all visits.
Liver fat percent. Measured in a subset (10 per group) by fast MRI technique
Outcome measures
| Measure |
Normal Weight
n=12 Participants
Normal Weight by BMI. No treatment.
|
Obese - NT
n=6 Participants
Obese by BMI. These participants were not assigned an intervention (non-treated).
|
Obese - Placebo
n=5 Participants
Dosage form: Stamped placebo pill to look like the 1000 mg metformin pill Dosage: 1 pill taken orally twice daily Duration: From early puberty (Tanner 3-4) until puberty completion (Tanner 5), approximately 3 years
|
Obese - Metformin
n=6 Participants
Dosage form: Metformin 1000 mg tablets Dosage: 1000 mg by mouth twice daily Duration: From early puberty (Tanner 3-4) until puberty completion (Tanner 5), approximately 3 years
|
|---|---|---|---|---|
|
Liver Adipose
Baseline
|
1.376 percentage of liver mass
Standard Deviation 0.594
|
8.290 percentage of liver mass
Standard Deviation 7.177
|
13.765 percentage of liver mass
Standard Deviation 5.457
|
8.290 percentage of liver mass
Standard Deviation 7.177
|
|
Liver Adipose
Tanner 5
|
2.208 percentage of liver mass
Standard Deviation 0.637
|
8.219 percentage of liver mass
Standard Deviation 5.757
|
10.327 percentage of liver mass
Standard Deviation 8.023
|
8.291 percentage of liver mass
Standard Deviation 5.757
|
SECONDARY outcome
Timeframe: Baseline, Tanner (puberty) stage 4-average 1.5 years from baseline, Tanner (puberty) stage 5-average 2.5 yrs from baseline, 6 mos post-treatment-average 3 yrs from baselinePopulation: 24 participants analyzed in the Obese NT Placebo group are also analyzed in the Obese Placebo group.
Please see primary outcome for more detail about timing of measurement.
Outcome measures
| Measure |
Normal Weight
n=47 Participants
Normal Weight by BMI. No treatment.
|
Obese - NT
n=37 Participants
Obese by BMI. These participants were not assigned an intervention (non-treated).
|
Obese - Placebo
n=24 Participants
Dosage form: Stamped placebo pill to look like the 1000 mg metformin pill Dosage: 1 pill taken orally twice daily Duration: From early puberty (Tanner 3-4) until puberty completion (Tanner 5), approximately 3 years
|
Obese - Metformin
n=20 Participants
Dosage form: Metformin 1000 mg tablets Dosage: 1000 mg by mouth twice daily Duration: From early puberty (Tanner 3-4) until puberty completion (Tanner 5), approximately 3 years
|
|---|---|---|---|---|
|
High Density Lipoprotein
Baseline
|
51.442 mg/dL
Standard Deviation 8.921
|
39.306 mg/dL
Standard Deviation 6.511
|
38.917 mg/dL
Standard Deviation 7.003
|
41.368 mg/dL
Standard Deviation 7.274
|
|
High Density Lipoprotein
Tanner 4
|
51.667 mg/dL
Standard Deviation 11.734
|
39.455 mg/dL
Standard Deviation 9.533
|
39.455 mg/dL
Standard Deviation 9.533
|
42.273 mg/dL
Standard Deviation 4.735
|
|
High Density Lipoprotein
Tanner 5
|
46.909 mg/dL
Standard Deviation 8.498
|
38.944 mg/dL
Standard Deviation 8.755
|
39.333 mg/dL
Standard Deviation 8.897
|
43.000 mg/dL
Standard Deviation 5.916
|
|
High Density Lipoprotein
Post-Puberty
|
NA mg/dL
Standard Deviation NA
Not Measured
|
NA mg/dL
Standard Deviation NA
Not Measured
|
40.923 mg/dL
Standard Deviation 8.645
|
41.818 mg/dL
Standard Deviation 8.171
|
Adverse Events
Obese - Metformin
Serious events: 0 serious events
Other events: 11 other events
Deaths: 0 deaths
Obese - Placebo
Serious events: 0 serious events
Other events: 14 other events
Deaths: 0 deaths
Normal Weight (No Treatment)
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Obese (No Treatment)
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Obese - Metformin
n=20 participants at risk
Dosage form: Metformin 1000 mg tablets Dosage: 1000 mg by mouth twice daily Duration: From early puberty (Tanner 3-4) until puberty completion (Tanner 5), approximately 3 years
Metformin: After randomization, the study drug (metformin or placebo) is gradually titrated to full dose of 1000 mg BID (or to maximum tolerated, at least 500 mg BID) over a period of 4 weeks to minimize adverse gastrointestinal effects. Participants are seen every three months to measure compliance and dispense new study drug. Every 6 months, they also have a physical examination in order to determine puberty staging. Study measurements (IVGTT, bloodwork, DXA) are performed at Tanner 4 puberty and Tanner 5 (puberty completion), at which time the study drug is stopped. Study measurements will be performed again 6 months after study drug is completed to assess if effects are persistent after study drug is stopped. During the treatment period, all participants receive standard lifestyle counseling.
|
Obese - Placebo
n=24 participants at risk
Dosage form: Stamped placebo pill to look like the 1000 mg metformin pill Dosage: 1 pill taken orally twice daily Duration: From early puberty (Tanner 3-4) until puberty completion (Tanner 5), approximately 3 years
|
Normal Weight (No Treatment)
n=47 participants at risk
Normal Weight by BMI. No treatment.
|
Obese (No Treatment)
n=13 participants at risk
Obese by BMI. These participants were not prescribed any intervention (Non-treated).
|
|---|---|---|---|---|
|
Gastrointestinal disorders
Bloating
|
35.0%
7/20 • Adverse event data were collected at each med visit approximately every 6 months
|
29.2%
7/24 • Adverse event data were collected at each med visit approximately every 6 months
|
0.00%
0/47 • Adverse event data were collected at each med visit approximately every 6 months
|
0.00%
0/13 • Adverse event data were collected at each med visit approximately every 6 months
|
|
Gastrointestinal disorders
Nausea
|
35.0%
7/20 • Adverse event data were collected at each med visit approximately every 6 months
|
45.8%
11/24 • Adverse event data were collected at each med visit approximately every 6 months
|
0.00%
0/47 • Adverse event data were collected at each med visit approximately every 6 months
|
0.00%
0/13 • Adverse event data were collected at each med visit approximately every 6 months
|
|
Gastrointestinal disorders
Diarrhea
|
30.0%
6/20 • Adverse event data were collected at each med visit approximately every 6 months
|
41.7%
10/24 • Adverse event data were collected at each med visit approximately every 6 months
|
0.00%
0/47 • Adverse event data were collected at each med visit approximately every 6 months
|
0.00%
0/13 • Adverse event data were collected at each med visit approximately every 6 months
|
Additional Information
Dr. Megan Kelsey
University of Colorado School of Medicine
Phone: 720-777-0991
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place