UKPDS 34 1998.

Study characteristics
Methods	Study design: parallel RCT
Participants	Inclusion criteria: newly‐diagnosed T2DM patients, age between 25 to 65 years inclusive, FPG > 6 mmol/L on two mornings, 1 to3 weeks apart, > 120% of ideal bodyweight. After 3 months dietary run‐in period FPG was between 6.1 mmol/L to 14.9 mmol/L Exclusion criteria: ketonuria > 3 mmol/L, history of myocardial infarction in the previous year, current angina or heart failure, more than one major vascular episode, serum creatinine > 175 µmol/L, severe retinopathy requiring photocoagulation, malignant hypertension, an uncorrected endocrine abnormality, an occupation which would not allow randomisation to insulin therapy (e.g. heavy goods vehicle driver), severe concurrent illness likely to limit life (e.g. cancer) or requiring extensive systemic treatment (e.g. ulcerative colitis), inadequate comprehension to allow co‐operation Diagnostic criteria: FPG > 6 mmol/L on two occasions
Interventions	Intervention(s): metformin Comparator(s): glibenclamide, insulin Duration of intervention: 10.7 years Duration of follow‐up: 10.7 years Run‐in period: 3 months Number of study centres: 15
Outcomes	Reported outcome(s) in full text of publication: glycaemic variables, safety
Study details	Trial identifier: — Trial terminated early: no
Publication details	Language of publication: English Funding: commercial funding and non‐commercial funding Publication status: peer‐reviewed journal/full article
Stated aim for study	Quote from publication: "This study investigated whether intensive glucose control with metformin has any specific advantage or disadvantage."
Notes	We have not included data from the conventional intervention arm in the UKPDS, as it had another glycaemic target. We have not included the chlorpropamide intervention arm, as this drug is no longer used in clinical practice
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote from publication: "Randomisation was by means of centrally produced, computer‐generated therapy allocations in sealed, opaque envelopes which were opened in sequence." Comment: method of random sequence generation adequately described
Allocation concealment (selection bias)	Low risk	Quote from publication: "Randomisation was by means of centrally produced, computer‐generated therapy allocations in sealed, opaque envelopes which were opened in sequence." Comment: method of allocation concealment adequately described
Blinding of participants and personnel (performance bias) severe hypoglycaemia	Low risk	Quote from publication: "The trial was open once patients were randomised" Comment: self‐reported outcome measurement, however, outcome not judged to be influenced by a lack of blinding
Blinding of outcome assessment (detection bias) severe hypoglycaemia	Low risk	Quote from publication: "Members of the UKPDS end‐point committee, who were unaware of assignments to study groups, adjudicated outcomes.." Comment: adjudicated outcome measurement, adequate blinding
Selective reporting (reporting bias)	High risk	Quote from publication: "The response to metformin therapy in the obese subjects is assessed by comparison with those allocated to diet policy and to sulphonylurea therapy." Comment: the publications only report a few outcomes for the comparison metformin versus sulphonylurea, and not for all outcomes as prespecified
Other bias	Unclear risk	Comment: received funding from pharmaceutical company. Factorial design (randomisation to blood pressure control) ‐ no test of interaction