Harnessing the weight-regulating properties of glucagon-like peptide-1 in the treatment of type 2 diabetes

The prevalence and incidence of type 2 diabetes are progressively increasing because of a concomitant rise in the prevalence of obesity. Intentional weight loss in patients with type 2 diabetes has been associated with a 25% reduction in total mortality and a 28% reduction in cardiovascular disease and diabetes mortality (1). Weight gain is not only a risk factor for development of type 2 diabetes, but it is also the undesirable feature of several current antidiabetic treatments such as thiazolidinediones, sulfonylureas, and insulin, with an estimated 2-kg weight gain for every 1% decrease inHbA1c). Reasons for this include defensive snacking to treat or prevent hypoglycemia, decreased glucosuria, decreased basal metabolic rate, and expansion in adipose tissue and fluid retention.Recently, novel therapeutic agents were developed for the treatment of type 2 diabetes. Among these are the incretin based therapies, which include glucagon like peptide (GLP)-1 receptor agonists and inhibitors of the protease dipeptidyl peptidase (DPP)-4. Both classes of drugs use the antidiabetic properties of GLP-1, an incretin hormone that potentiates insulin secretion in a glucose-dependent manner.