Sibutramine is effective for weight loss and diabetic control in obesity with type 2 diabetes: a randomised, double-blind, placebo-controlled study

Aims: To assess the efficacy and tolerability of sibutramine 15 mg once dai ly as a weight reduction agent in overweight and obese patients (body mass index (b.m.i.) > 26 kg/m(2)) with type 2 diabetes when given with a customi sed, reduced-calorie diet, and to evaluate the influence of weight loss on diabetic control. Methods: Randomised, placebo-controlled, double-blind, parallel-group, 12-w eek study conducted at two hospital-based obesity/diabetes clinics. Patient s were men and women aged 30-65 years, with b.m.i. > 26 kg.m(2) and less th an or equal to 35 kg/m(2) and treated or untreated type 2 diabetes diagnose d greater than or equal to 6 months previously, Each patient was given sibu tramine 15 mg or placebo once daily and advised to follow a customised diet of 500 kcal/day less than the individual's energy needs. The principal mea sure of efficacy was change in body weight (b.w.). Additional efficacy meas urements were changes in b.m.i., body composition as measured by dual-energ y X-ray absorptiometry, and change in waist and hip measurements. Changes i n diabetic control were assessed by blood glucose levels fasting and after a standard test meal, fasting insulin level. and glycosylated haemoglobin l evel. Adverse events (AEs) were monitored at each visit, and routine labora tory safety tests were done at 4-week intervals. Results: Ninety-one patients were randomised into the study, 44 to placebo and 47 to sibutramine 15 mg once daily, Eighty-three patients (91%) complet ed the study, 40 (91%) on placebo and 43 (91%) on sibutramine. Mean weight reduction from baseline was statistically significantly greater with sibutr amine than with placebo at every measurement and at the end of the study (2 .4 vs. 0.1 kg at week 12; p < 0.001: intent-to-treat). The proportion of pa tients who lost > 5% of their baseline b.w. was 19% in the sibutramine grou p and 0% in the placebo group (p < 0.001; 95% confidence interval: 9, 30), Patients receiving sibutramine lost significantly more fat mass compared wi th those receiving placebo, as a percentage (1.0% vs. 0.1%; p < 0.05) and i n absolute terms (1.8 vs. 0.2 kg, p < 0.001), Loss of lean mass was not sig nificantly different between the groups. Mean peak blood glucose concentrat ion after a standard test meal decreased by 1.1 mmol/l in the sibutramine t reatment group but increased by 0.5 mmol/l in the placebo group (p = 0.04; difference in means, 1.6, 95% confidence interval: -3.3, -0.1). Mean fastin g blood glucose decreased by 0.3 mmol/l with sibutramine and increased by 1 .4 mmol/l with placebo. Mean glycosylated haemoglobin levels decreased by 0 .3% units with sibutramine treatment, and were unchanged with placebo. Howe ver, more sibutramine-treated patients (33%) than placebo-treated patients (5%) achieved decreases in glycosylated haemoglobin of 1% unit or more (p < 0.05). Sibutramine 15 mg was safe and well tolerated, and AEs were mostly mild or moderate in severity. No significant differences were found between treatment groups in blood pressure. No clinically significant conduction o r rhythm abnormalities were observed on EGG. Conclusions: Sibutramine 15 mg once daily with a customised, reduced-calori e diet significantly reduced weight compared with placebo in overweight and obese patients (b.m.i. > 26 kg/m(2)) with type 2 diabetes, Sibutramine was well tolerated, and significant improvement in diabetic control was seen i n conjunction with weight reduction on sibutramine treatment.