Rosiglitazone reduced type 2 diabetes but increased heart failure in patients with impaired glycemic control.

M e t h o d s Design: Randomized placebo-controlled trial (Diabetes Reduction Assessment with ramipril and rosiglitazone Medication [DREAM]). Allocation: Concealed.* Blinding: Blinded (clinicians, patients, data collectors, and outcome assessors).* Follow-up period: Median 3.0 years (range 2.5 to 4.7 y). Setting: 191 sites in 21 countries. Patients: 5269 patients (mean age 55 y, 59% women) who had impaired fasting glucose (14%), impaired glucose tolerance (57%), or both (29%). Exclusion criteria were history of diabetes (except gestational diabetes), cardiovascular (CV) disease, or intolerance to angiotensin-converting enzyme inhibitors or thiazolidinediones (TZDs). Intervention: Rosiglitazone, 4 mg once daily for 2 months and then 8 mg once daily (n = 2635), or placebo (n = 2634). At baseline and follow-up visits, all patients received advice from research staff about healthy diets and lifestyle habits to reduce diabetes. Outcomes: A composite outcome of death from any cause or diagnosis of diabetes. Secondary outcomes included regression to normal fasting and 2-hour postload glucose levels (fasting plasma glucose level < 6.1 mmol/L and 2-h plasma glucose level < 7.8 mmol/L), a composite of CV events (myocardial infarction, stroke, CV death, revascularization procedures, heart failure, new angina with evidence of ischemia, or ventricular arrhythmia needing resuscitation), individual components of the CV composite endpoint, and renal events and a composite cardiorenal endpoint. Patient follow-up: 98% (intention-to-treat analysis).