Besides
genetic predisposition,
obesity is the most important risk factor for the development of
type 2 diabetes mellitus. Even modest
weight reduction can improve
blood glucose control in
overweight subjects. After failure of lifestyle modifications,
antiobesity drugs such as
orlistat, a potent and selective inhibitor of gastric and pancreatic lipases that reduces
lipid intestinal absorption, or
sibutramine, a
noradrenaline and
5-hydroxytryptamine reuptake inhibitor that regulates food intake, may be considered to favour
weight loss and/or weight maintenance. Several placebo-controlled studies have recently demonstrated that both drugs are able to promote
weight loss in obese type 2 diabetic patients treated with diet alone, sulphonylureas,
metformin or
insulin. The greater
weight reduction as compared to placebo was associated with a significant reduction of glycated haemoglobin levels and/or of the doses of classical antihyperglycaemic agents, especially in good responders who lost at least 10% of initial
body weight. In addition, vascular risk factors associated to
insulin resistance were also reduced after
weight loss. These
antiobesity agents may also contribute to delay or prevent the progression from
impaired glucose tolerance to overt
type 2 diabetes in at risk obese individuals ("
Xenical in the prevention of diabetes in obese subjects" trial). Large long-term prospective studies, such as the "
Sibutramine cardiovascular and diabetes outcome study" should better determine the place of pharmacological anti-
obesity strategy in the overall management of obese patients with
impaired glucose tolerance or
type 2 diabetes.