Weight loss with sibutramine improves glycaemic control and other metabolic parameters in obese patients with type 2 diabetes mellitus

Aim: To determine the efficacy and tolerability of sibutramine hydrochlorid e in obese patients whose type 2 diabetes was poorly controlled on diet alo ne or with an oral antidiabetic agent Methods: This study was a 24-week, double-blind, multicentre trial followin g a B-week placebo run-in period. One hundred and seventy-five obese (body mass index (b.m.i.) greater than or equal to 27 kg/m(2)) patients with poor ly controlled type 2 diabetes mellitus were randomized either to sibutramin e (n = 89; mean age 53.5 years; mean weight 99.3 kg) or placebo (n = 86; me an age 55 years; mean weight 98.2 kg) at 16 participating centres. To achie ve moderate calorie restriction (deficit greater than or equal to 250-500 k cal/day), individual dietary counselling was accompanied by either placebo or sibutramine (initial dosage of 5 mg/day titrated up by 5 mg biweekly thr ough week 6, and maintained at 20 mg through week 24). The main outcome mea sures included changes in weight, b.m.i., waist and hip circumference, glyc aemic control, lipid profile, and quality of life, and evaluation of report ed adverse events. Results: Sixty-seven per cent of sibutramine patients and 71% of placebo pa tients completed the study. At week 24 when comparing those who completed t he course, sibutramine compared with placebo patients showed significantly greater (p < 0.001) absolute (-4.3 vs. -0.4 kg) and percentage (-4.5% vs. - 0.5%) weight loss. Weight loss greater than or equal to 5% or 10% was achie ved by 33% and 8% of sibutramine patients, respectively, but no placebo pat ients (p < 0.03 or better). Improvement in glycaemic control was correlated with weight loss (p < 0.001). In 5% and 10% weight-loss responders, mean t reatment differences were -0.53% and -1.65% (p less than or equal to 0.05), respectively, for HbA(1c), and -1.4 mmol/l (p less than or equal to 0.05) and -3.8 (p less than or equal to 0.05) mmol/l for fasting plasma glucose. Sibutramine patients also showed improvements in fasting insulin, triglycer ides, HDL cholesterol, and quality-of-life assessments. Overall, sibutramin e was well tolerated compared with the placebo. Sibutramine treatment was a ssociated with small mean increases in blood pressure (BP) and pulse, altho ugh an increase in BP was not seen in sibutramine-treated patients who lost greater than or equal to 5% of their weight. Conclusions: Sibutramine produced statistically and clinically significant weight loss when used in combination with recommendations for moderate calo ric restriction. This weight loss was associated with improvements in metab olic control and quality of life, and sibutramine was generally well tolera ted in obese patients with type 2 diabetes.