Incretins as new therapeutic targets of type 2 diabetes

The epidemic characteristics of type 2 diabetes mellitus (DM) pose a formidable challenge in terms of healthcare, given the tremendous impact it has on the healthcare resources needed not only to treat it, but also to prevent and treat the associated cardiovascular complications. This makes up the number I cause of DM-associated morbidity-mortality in addition to its social and personal impact. We currently have a growing number of available treatment tools that make it possible to achieve the target glycemic control in most of our patients, albeit unfortunately, only temporarily in a good many of them, because of the progressive nature of the disease. Furthermore, current therapy often entails undesirable effects, such as weight gain or the emergence of hypoglycemias that limit their optimization. Recently, a new class of drugs has been incorporated into the treatment of DM incretin mimetics. These new drugs act in very much the same way as the intestinal hormones that are naturally secreted following the intake of nutrients, called incretins (e.g., glucagon like peptide-1 [GLP-1]), with the added advantage that these molecules are resistant to enzymatic degradation by the DPP-lV enzyme. This provides them with a half-life that makes ambulatory treatment possible, unlike natural incretins whose half-life is too short to make them viable as treatment. The incretin mimetics bind to GLP-1 receptors, increasing glucose-dependent secretion of insulin and decreasing glucose-dependent posprandial secretion of glucagon, slowing gastric emptying, and reducing food intake. All these mechanisms have a significant impact on glucose homeostasis and a beneficial effect on body weight. Moreover, studies in experimental models suggest that these new molecules might have a promising effect on pancreatic P cell function and mass. Exenatide is the first incretin mimetic available to date. Efficacy and safety data of this drug show it as a therapeutic option for the treatment of type 2 DM.