Freemark 2001.

Methods	Parallel randomised controlled clinical trial, randomisation ratio 1:1, superiority design
Participants	Inclusion criteria: aged 12 to 19 years and had a BMI > 30 kg/m2. Criteria for enrolment included: a fasting insulin concentration > 15 mU/mL ≥ 1 first‐ or second‐degree relative (parent, sibling or grandparent) with type 2 diabetes Exclusion criteria: ‐ Diagnostic criteria: see above
Interventions	Intervention: metformin Comparator: placebo Number of trial centres: 1 Treatment before trial: none Titration period: no
Outcomes	Outcomes reported in abstract of publication: BMI, serum leptin, fasting blood glucose, fasting insulin levels, insulin sensitivity, glucose effectiveness, haemoglobin A1c, serum lipids, serum lactate, adverse events
Study details	Run‐in period: 48 hours' inpatient tests Trial terminated early: no
Publication details	Language of publication: English Commercial funding and noncommercial funding Publication status: peer‐reviewed journal
Stated aim for study	Quote from publication: "We reasoned that drugs that increase glucose tolerance in diabetic patients might prove useful in preventing the progression to glucose intolerance in high‐risk patients"
Notes
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "patients were randomized to the metformin and placebo groups by a research pharmacist using computer‐generated randomization tables" Comment: an appropriate randomisation method was used
Allocation concealment (selection bias)	Low risk	Quote: "the allocation was made by the research pharmacist at the first medication visit. The pill bottles were coded ‐ thus the pharmacist was blinded to the medication" Comment: author confirmed allocation was concealed
Blinding of participants and personnel (performance bias) Objective outcomes	Low risk	Quote: "We conducted a double‐blind, placebo‐controlled study" Comment: author confirmed all participants and trial personnel were blinded
Blinding of participants and personnel (performance bias) Subjective outcomes	Low risk	Quote: "We conducted a double‐blind, placebo‐controlled study" Comment: author confirmed all participants and trial personnel were blinded
Blinding of outcome assessment (detection bias) Objective outcomes	Low risk	Quote: "We conducted a double‐blind, placebo‐controlled study" Comment: author confirmed all participants and trial personnel were blinded
Blinding of outcome assessment (detection bias) Subjective outcomes	Low risk	Quote: "We conducted a double‐blind, placebo‐controlled study" Comment: author confirmed all participants and trial personnel were blinded
Incomplete outcome data (attrition bias) Objective outcomes	Unclear risk	Comment: a missing data method was not used; however, dropout rates were fairly low
Incomplete outcome data (attrition bias) Subjective outcomes	Unclear risk	Comment: a missing data method was not used; however, dropout rates were fairly low
Selective reporting (reporting bias)	Unclear risk	Comment: since no protocol was published before trial was completed, it is unclear whether all outcomes were reported
Other bias	High risk	Quote: "the study involved a small number of patients and the results must be confirmed in a larger sample" Comment: the trial did not perform a power calculation and the sample size was small. It is likely the trial was underpowered. Potential influence of a commercial funding source. Baseline differences identified and not adjusted for in the analysis