A Randomized Trial of Sibutramine in the Management of Obese Type 2 Diabetic Patients Treated With Metformin
- Steven J. McNulty, MD1,
- Ehud Ur, MB, FRCP2,
- Gareth Williams, MD, FRCP Edin1 and
- For the Multicenter Sibutramine Study Group
- 1Diabetes and Endocrinology Research Group, Department of Medicine, University Hospital Aintree, Liverpool, U.K
- 2Division of Endocrinology, Dalhousie University, Halifax, Canada
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/m2 were studied. Changes were assessed in weight, blood pressure and resting heart rate, HbA1c, 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 ≥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 ≥10% weight showed significant decreases in both HbA1c (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 ≥10% (a 29% decrease, P < 0.01). Treatment was generally well tolerated. Sibutramine treatment raised sitting diastolic blood pressure by ≥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 ≥10% weight. Pulse rate increased significantly more with sibutramine, being ≥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.
Address correspondence and reprint requests to Professor Gareth Williams, Diabetes and Endocrinology Research Group, Department of Medicine, University Hospital Aintree, Longmoor Lane, Liverpool L9 7AL, U.K. E-mail:.
Received for publication 10 August 2001 and accepted in revised form 30 September 2002.
E.U. has received honoraria for speaking engagements from GlaxoSmithKline, Novartis, Abbott, and Roche. G.W. has received honoraria for speaking engagements and for acting as an advisor for and has received research support from Knoll Pharmaceuticals.
A table elsewhere in this issue shows conventional and Système International (SI) units and conversion factors for many substances.
- DIABETES CARE