While antidiabetes therapies target glycemic control, most do not address the underlying problems of excess bodyweight and deteriorating pancreatic beta-cell function. Some therapies also provoke hypoglycemia and/or weight gain. Glucagon-like peptide-1 (GLP-1) is an incretin hormone secreted by the gut in response to nutrient intake and has a major role in the post-prandial insulin response in healthy individuals. The incretin response is, however, impaired in individuals with type 2 diabetes. There are two therapeutic approaches that target the incretin system: GLP-1 receptor agonists and dipeptidyl peptidase-4 (DPP-4) inhibitors. GLP-1 receptor agonists provide pharmacological levels of GLP-1 activity, while DPP-4 inhibitors restore physiological levels. The pharmacological levels of GLP-1 induced by GLP-1 receptor agonists provide effective glycemic control and weight reduction. The DPP-4 inhibitors also improve glycemic control but are weight-neutral. Pre-clinical studies in animal models andin vitrosystems suggest that incretin-based therapies have the potential to preserve beta-cell mass and improve their function. Initial clinical data show improvements in beta-cell function in patients treated with incretin-based therapies, supporting the pre-clinical observations. A further benefit of incretin-based therapies is that they provide glucose-dependent glucose control, which means that they have a low inherent risk of inducing hypoglycemia. These agents therefore look extremely promising in the management of type 2 diabetes, being efficacious and having positive benefits on weight, low risk of hypoglycemia, and the potential to improve pancreatic islet cell function in the long term.
Effect of sitagliptin on glycemic control and beta cell function in Japanese patients given basal-supported oral therapy for type 2 diabetes
