OBJECTIVE: To evaluate the effects of sibutramine (15 and 20 mg/day) on weight, metabolic control, and blood pressure in metformin-treated obese subjects with type 2 diabetes. RESEARCH DESIGN AND METHODS: A 12-month randomized prospective placebo-controlled double-blind study was performed. It included 21 primary and secondary care centers in England, Canada, France, and Belgium. A total of 195 subjects (44% male) with type 2 diabetes and a BMI >27 kg/m(2) were studied. Changes were assessed in weight, blood pressure and resting heart rate, HbA(1c), fasting glucose, and lipids. RESULTS: Sibutramine induced significant weight loss (P < 0.001) with both 15 mg/day (5.5 +/- 0.6 kg at 12 months) and 20 mg/day (8.0 +/- 0.9 kg), whereas placebo did not (0.2 +/- 0.5 kg). Weight loss > or = 10% was achieved by 14 and 27% of subjects receiving 15 and 20 mg, respectively, but by none given placebo. Glycemic control improved in parallel with weight loss, and subjects who lost > or = 10% weight showed significant decreases in both HbA(1c) (1.2 +/- 0.4%, P < 0.0001) and fasting plasma glucose (1.8 mmol/l, P < 0.001). HDL cholesterol increased slightly with the higher dose, whereas plasma triglycerides fell with both doses, especially in subjects with weight loss of > or = 10% (a 29% decrease, P < 0.01). Treatment was generally well tolerated. Sibutramine treatment raised sitting diastolic blood pressure by > or = 5 mmHg in a higher proportion of patients than did placebo (43% with 15 mg/day vs. 25% with placebo, P < 0.05), but this effect was less evident in subjects who had a weight loss of > or = 10% weight. Pulse rate increased significantly more with sibutramine, being > or = 10 bpm higher in 42% of treated patients versus 17% with placebo (P < 0.01). CONCLUSIONS: Sibutramine can be an effective adjunct to metformin treatment in selected obese type 2 diabetic subjects and improves metabolic control in individuals who lose weight.