UKPDS Study 1991.

Methods	Study design: parallel RCT Study design (recruitment): 1977 to 1991 Follow‐up period: 120 months
Participants	Country: UK Setting: multicentre (28) Patients aged 25 to 65 with new diagnosed type 2 diabetes; fasting plasma glucose > 6 mmol/L on two mornings, 1 to 3 weeks apart Number: treatment group (2729); control group (1138) Mean age ± SD (years): treatment group (53.2 ± 8.6); control group (53.4 ± 8.6) Sex (M/F): treatment group (649/444); control group (705/433) Exclusion criteria: ketonuria > 3 mmol/L; SCr > 175 μmol/L; myocardial infarction in the previous year; current angina or heart failure; more than one major vascular event; retinopathy requiring laser treatment; malignant hypertension; uncorrected endocrine disorder; occupation that precluded insulin therapy (e.g., driver of heavy goods vehicle); severe concurrent illness that would limit life or require extensive systemic treatment; inadequate understanding; unwillingness to enter the study
Interventions	Treatment group Intensive treatment Control group Conventional treatment
Outcomes	Any diabetes‐related endpoint (sudden death, death from hyperglycaemia or hypoglycaemia, fatal or non‐fatal myocardial infarction, angina, heart failure, stroke, kidney failure, amputation (of at least one digit), vitreous haemorrhage, retinal photocoagulation, blindness in one eye, or cataract extraction) Diabetes‐related death (death from myocardial infarction, stroke, peripheral vascular disease, kidney disease, hyperglycaemia or hypoglycaemia, and sudden death) All‐cause mortality Myocardial infarction (fatal and non‐fatal) and sudden death Stroke (fatal and non‐fatal); amputation or death due to peripheral vascular disease Microvascular complications (retinopathy requiring photocoagulation, vitreous haemorrhage, and or fatal or non‐fatal kidney failure)
Notes	Funding source: Novo­Nordisk, Bayer, Bristol­Myers Squibb, Hoechst,Lilly, Lipha, and Farmitalia Carlo Erba. GlaxoWellcome, Smith­Kline Beecham, Pfizer, Zeneca, Pharmacia and Upjohn, and Roche
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Randomisation was by means of centrally produced, computer‐generated therapy allocations
Allocation concealment (selection bias)	Low risk	Sealed opaque envelopes
Blinding of participants and personnel (performance bias) All outcomes	Unclear risk	Insufficient information to permit judgement
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	Not centrally determined outcome measurements
Incomplete outcome data (attrition bias) All outcomes	Low risk	47/1148 lost to follow‐up (4%)
Selective reporting (reporting bias)	Low risk	All expected outcomes reported
Other bias	High risk	Funded by Pharma