A randomized study of orlistat in combination with a weight management programme in obese patients with Type 2 diabetes treated with metformin.

AIMS: To assess the effects of orlistat vs. placebo, in combination with a weight management programme, on weight loss and metabolic control in obese patients with Type 2 diabetes.

METHODS: Patients treated with either metformin alone or metformin in combination with sulphonylurea were randomized to double-blind treatment with orlistat or placebo (120 mg) three times daily, combined with a mildly reduced calorie diet and a weight management programme for 52 weeks. Changes in body weight, anthropometry, glycaemic control and lipid profile were assessed.

RESULTS: After 52 weeks, orlistat-treated patients achieved an almost threefold greater reduction in weight compared with placebo recipients (-5.0% vs. -1.8%; P<0.0001). The decrease in waist circumference was significantly greater with orlistat than placebo (-4.8 cm vs. -2.8 cm; P=0.0022). Orlistat treatment was also associated with significantly greater reductions in haemoglobin A(1c) (-1.1% vs. -0.2%; P<0.0001), fasting plasma glucose (-1.9 mmol/l vs. -0.3 mmol/l; P<0.0001), total cholesterol (-0.2 mmol/l vs. 0.1 mmol/l; P=0.03) and apolipoprotein B (-0.08 g/l vs. 0.01 g/l; P=0.0085) and greater improvements in beta-cell function (P=0.031) and insulin resistance (P=0.001) assessed using the homeostasis model assessment (HOMA). Similar results were obtained for subgroups of patients treated with metformin alone or metformin in combination with sulphonylurea. Orlistat treatment reduced the requirement for anti-diabetic medication more than placebo.

CONCLUSIONS: Orlistat, in combination with a reduced calorie diet and a weight management programme, promotes weight loss and clinically relevant improvements in glycaemic control and other cardiovascular risk factors in obese patients with Type 2 diabetes.