Pharmacological intervention: the antiobesity approach.

Reduction in overweight and obesity management have been shown to be important in the treatment of diabetes. Even modest weight loss produces important metabolic benefits if maintained over the long term. Thus a pharmacotherapeutic agent that could produce a maintained weight loss, and had a good safety profile, would revolutionize the treatment of type II (non-insulin-dependent) diabetes. Two obesity management agents, orlistat and sibutramine, are expected shortly for the long-term treatment of obesity. These agents have been shown to be effective in 1-2-year-long studies in obese, non-diabetic patients. They produced significant improvements in weight loss compared with placebos. The efficacy of these obesity management agents has also been demonstrated in short-term studies in patients with type II diabetes. As yet, however, few studies have investigated the long-term effects of these treatments in diabetic patients. Obese patients with type II diabetes receiving 12 months of dexfenfluramine therapy showed greater reductions in weight, fasting blood glucose and HbA1c levels than the controls. A 1-year study of orlistat treatment for patients with type II diabetes revealed substantial benefits in glycaemic control, even though weight loss was only moderate. A 1-year treatment with orlistat also substantially prevented the conversion of impaired glucose tolerance into type II diabetes (conversion rate 2.6% in the orlistat group versus 10.4% in the placebo group). Encouraging results have also been reported from studies on orlistat and sibutramine in non-diabetics, with beneficial effects seen for weight loss and other diabetes risk factors. Antiobesity pharmacotherapy therefore appears to offer a realistic option for the prevention of diabetes, although further studies are required to determine its efficacy.