Wilson 2010.

Methods	Parallel randomised controlled clinical trial, randomisation ratio 1:1, superiority design
Participants	Inclusion criteria: BMI ≥ 95th percentile for age and sex but weighed < 136 kg (weight limit for DEXA table) Exclusion criteria: previous diagnosis of diabetes mellitus had ever used a medication to treat diabetes or insulin resistance or weight loss were taking any medications known to increase metformin levels received recent glucocorticoid therapy had any identified syndrome or medical disorder predisposing to obesity had surgical therapy of obesity attended formal weight loss programme in last 6 months had significant alcohol use in last 6 months had elevated creatinine or liver enzymes had untreated disorders of the thyroid impaired mobility had ever been pregnant Diagnostic criteria: see above
Interventions	Intervention: metformin + lifestyle intervention programme Comparator: placebo + lifestyle intervention programme Number of trial centres: 6 Treatment before trial: 4‐week placebo run‐in phase, during which participants were required to attend at least 2 of 3 scheduled lifestyle modification sessions and demonstrate 80% compliance with daily placebo treatment (pill count) for subsequent randomisation Titration period: participants either given metformin XR or identical placebo tablets and instructed to take 1 tablet/day (metformin hydrochloride XR 500 mg or placebo) orally before dinner for 2 weeks, then 2 tablets/day for 2 weeks, then 4 tablets/day from week 8 to week 52
Outcomes	Outcomes reported in abstract of publication: mean adjusted BMI, body compositions, abdominal fat, insulin indices
Study details	Run‐in period: 4‐week placebo run‐in phase (see above) Trial terminated early: no
Publication details	Language of publication: English Noncommercial funding Publication status: peer‐reviewed journal
Stated aim for study	Quote from publication: "to test the hypothesis that 48 weeks of daily metformin hydrochloride extended release (EX) will reduce body mass index in obese adolescents, as compared with placebo"
Notes
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "Subjects who successfully completed the run‐in period were randomized to metformin XR or placebo treatment according to random sequences constructed at the Data Coordinating Center. To ensure balance across major factors, the randomization was stratified by site and sex" "To ensure nonpredictability of assignment, the randomization sequence was grouped in randomly permuted blocks of 2 and 4, and assignments were randomly permuted within block" Comment: an adequate randomisation method was used
Allocation concealment (selection bias)	Low risk	Quote: "Subjects who successfully completed the run‐in period were randomized to metformin XR or placebo treatment according to random sequences constructed at the Data Coordinating Center" Comment: adequate allocation concealment
Blinding of participants and personnel (performance bias) Objective outcomes	Low risk	Quote: "Subjects and study personnel were blinded to assignment throughout the entire study" Comment: performance bias likely to be reduced by blinding participants and trial personnel
Blinding of participants and personnel (performance bias) Subjective outcomes	Low risk	Quote: "Subjects and study personnel were blinded to assignment throughout the entire study" "Unblinded data were seen only by the Data and Safety Monitoring Board and study statistician" Comment: performance bias likely to be reduced by blinding participants and trial personnel
Blinding of outcome assessment (detection bias) Objective outcomes	Low risk	Quote: "Subjects and study personnel were blinded to assignment throughout the entire study" "Unblinded data were seen only by the Data and Safety Monitoring Board and study statistician" Comment: outcomes assessors blinded
Blinding of outcome assessment (detection bias) Subjective outcomes	Low risk	Quote: "Subjects and trial personnel were blinded to assignment throughout the entire study" "Unblinded data were seen only by the Data and Safety Monitoring Board and study statistician" Comment: outcomes assessors blinded
Incomplete outcome data (attrition bias) Objective outcomes	High risk	Quote: "Ninety‐two subjects were screened and 77 were randomized, 39 to metformin XR, 38 to placebo; 27 and 19 in each group were measured at weeks 52 and 100, respectively" Comment: dropout fairly high in each group and no imputation method was performed to replace missing data
Incomplete outcome data (attrition bias) Subjective outcomes	High risk	Quote: "Ninety‐two subjects were screened and 77 were randomized, 39 to metformin XR, 38 to placebo; 27 and 19 in each group were measured at weeks 52 and 100, respectively" Comment: dropout fairly high in each group and no imputation method was performed to replace missing data
Selective reporting (reporting bias)	Low risk	Comment: all outcomes reported
Other bias	Unclear risk	Comment: baseline means seemed to be adjusted