Kahn 2006.

Methods	DURATION OF INTERVENTION: 4.0 years (median) DURATION OF FOLLOW‐UP: 4.0 years (median) RUN‐IN PERIOD: 4 weeks, placebo + diet/exercise LANGUAGE OF PUBLICATION: English
Participants	WHO PARTCIPATED: people with recently diagnosed type 2 diabetes mellitus, treated with life style management only INCLUSION CRITERIA: eligible patients were between the ages of 30 and 75 years, with fasting plasma glucose levels ranging from 126 to 180 mg per deciliter (7.0 to 10.0 mmol per liter) while their only treatment was lifestyle management EXCLUSION CRITERIA: clinically significant hepatic disease, renal impairment, a history of lactic acidosis, unstable or severe angina, known congestive heart failure (CHF, New York Heart Association class I, II, III, or IV), or uncontrolled hypertension DIAGNOSTIC CRITERIA: "recently diagnosed (i.e., within 3 years)" CO‐MORBIDITIES: not stated CO‐MEDICATIONS: Antihypertensive therapy [no. (%)]: I1: 744 (51.1) C1: 737 (50.7) C2: 753 (52.3) Lipid‐lowering therapy [no. (%)] I1: 378 (26.0) C1: 377 (25.9) C2: 370 (25.7)
Interventions	NUMBER OF STUDY CENTRES: 488 COUNTRY/ LOCATION: United States, Canada, and 15 European countries SETTING: not stated INTERVENTION (DOSE/DAY): rosiglitazone (max 8 mg/day) CONTROL (DOSE/DAY): metformin (max 2g/day) glyburide (max 15 mg/day) TREATMENT BEFORE STUDY: diet/exercise TITRATION PERIOD: patients received initial daily doses of 4 mg of rosiglitazone, 500 mg of metformin, or 2.5 mg of glyburide for each drug, the dose was increased according to the protocol to the maximum daily effective dose (4 mg of rosiglitazone twice daily, 1 g of metformin twice daily, and 7.5 mg of glyburide twice daily a dose increase was required at each visit if the fasting plasma glucose level was 140 mg per deciliter or more; a dose reduction was permitted if adverse events occurred
Outcomes	PRIMARY OUTCOMES: time from randomization to treatment failure, which was defined as confirmed hyperglycemia (fasting plasma glucose level, >180 mg/dl) on consecutive testing after at least 6 weeks of treatment at the maximum‐dictated or maximum‐tolerated dose of the study drug an independent adjudication committee, whose members were unaware of assignments to treatment groups, used prespecified criteria (available at www.nejm.org) to determine whether the primary outcome was reached in cases in which a confirmatory fasting plasma glucose level had not been obtained, a patient had withdrawn because of an insufficient therapeutic effect, or an additional glucose lowering drug had been administered before the confirmation of hyperglycemia (according to a protocol amendment adopted in February 2004) the threshold of more than 180 mg per deciliter for confirmed hyperglycemia was selected to represent unequivocal failure in the maintenance of adequate glycemic control without incurring undue hyperglycemic symptoms; the threshold of a fasting plasma glucose level of more than 140 mg per deciliter for increasing the dose of a study drug reflected clinical guidelines at the time of study design. SECONDARY OUTCOMES: time from randomization to a confirmed fasting plasma glucose level of more than 140 mg per deciliter after at least 6 weeks of treatment at the maximum‐tolerated dose of a study drug (for patients who entered the study with a fasting plasma glucose level of 140 mg per deciliter or less) other prespecified outcomes were levels of fasting plasma glucose and glycated hemoglobin, weight, and measures of insulin sensitivity and beta‐cell function, as determined by homeostasis model assessment (HOMA 2) with the use of the HOMA calculator (www.dtu.ox.ac.uk) Secondary endpoints according to the published study protocol (Diabetes Care 2002): ‐ glycaemic control ‐ insulin sensitivity ‐ beta‐cell function ‐ cardiovascular risk markers ‐ renal function ‐ patient reported outcomes (quality of life) ‐ resource utilization (direct health care costs will be assessed as the number of emergency room visits, number of unscheduled visits to the study physician’s office, number of hospitalizations, and length of stay. Furthermore, indirect economic costs associated with bed days (days when patients stay in bed for half a day or more) and restricted activity days (days when patients reduce their usual activities, such as housework or shopping) will be evaluated) ‐ safety parameters (including hypoglycaemia)
Notes	AIM OF STUDY: to evaluate the durability of glycemic control in patients receiving monotherapy with rosiglitazone, metformin or glyburide zhe therapeutic goal was a fasting plasma glucose level below 140 mg/dl (7.8 mmol/L).
Risk of bias
Bias	Authors' judgement	Support for judgement
Allocation concealment?	Low risk	A ‐ Adequate