Srinivasan 2006.

Methods	Cross‐over randomised controlled clinical trial, randomisation ratio 1:1, superiority design
Participants	Inclusion criteria: aged 9 to 18 years referred to the endocrine clinic at The Children's Hospital at Westmead between March 2002 and March 2003 with obesity, as defined by the International Obesity Task Force, and clinical suspicion of insulin resistance, as defined by either a fasting insulin (milliunits per litre) to glucose (millimoles per litre) ratio > 4.5 (15) or the presence of acanthosis nigricans Exclusion criteria: known type 1 or type 2 diabetes mellitus, contraindications to metformin therapy or magnetic resonance imaging scanning (or both) and weight > 120 kg due to technical difficulties with DEXA scans Diagnostic criteria: see above
Interventions	Intervention: metformin + "standardised information on healthy eating and exercise" Comparator: placebo + "standardised information on healthy eating and exercise" Number of trial centres: 1 Treatment before trial: no Titration period: both metformin and placebo doses were gradually built up over a 3‐week period to a final dose of 1 g twice daily
Outcomes	Outcomes reported in abstract of publication: mean age, median BMI z score, weight, BMI, waist circumference, subcutaneous abdominal adipose tissue, fasting insulin
Study details	Run‐in period: no Trial terminated early: no
Publication details	Language of publication: English Noncommercial funding Publication status: peer‐reviewed journal
Stated aim for study	Quote from publication: "We assessed the effect of metformin on body composition and insulin sensitivity in pediatric subjects with exogenous obesity"
Notes	‐
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "Block randomization (blocks of four) with stratification by pubertal stage (Tanner 1‐2 or Tanner 3‐5) was performed by computer generated random number allocation" Comment: an adequate randomisation method was used
Allocation concealment (selection bias)	Low risk	Quote (from the author): "randomisation was performed in the hospital pharmacy by random number generation and only revealed for data analysis" Comment: allocation was likely concealed
Blinding of participants and personnel (performance bias) Objective outcomes	Low risk	Quote: "All participants and investigators were blinded to the intervention" Comment: participants and personnel were blinded
Blinding of participants and personnel (performance bias) Subjective outcomes	Low risk	Quote: "All participants and investigators were blinded to the intervention" Comment: participants and personnel were blinded
Blinding of outcome assessment (detection bias) Objective outcomes	Low risk	Quote: "All participants and investigators were blinded to the intervention" Comment: participants and personnel were blinded
Blinding of outcome assessment (detection bias) Subjective outcomes	Low risk	Quote: "All participants and investigators were blinded to the intervention" Comment: participants and personnel were blinded
Incomplete outcome data (attrition bias) Objective outcomes	Unclear risk	Comment: an imputation method was not used to replace missing data; however, dropout rates were fairly low
Incomplete outcome data (attrition bias) Subjective outcomes	Unclear risk	Comment: an imputation method was not used to replace missing data; however, dropout rates were fairly low
Selective reporting (reporting bias)	Unclear risk	Comment: the publication did not report raw data for some of the outcomes, but a clinical trial entry was available and there were no differences
Other bias	Unclear risk	Comment: no power calculation was performed; therefore, the trial may have been underpowered