New Approaches to Feline Diabetes Mellitus: Glucagon-like peptide-1 analogs

Clinical relevance: Incretin-based therapies are revolutionizing the field of human diabetes mellitus (DM) by replacing insulin therapy with safer and more convenient long-acting drugs. Mechanism of action: Incretin hormones (glucagon-like peptide-1 [GLP-1] and glucose-dependent insulinotropic peptide [GIP]) are secreted from the intestinal tract in response to the presence of food in the intestinal lumen. GLP-1 delays gastric emptying and increases satiety. In the pancreas, GLP-1 augments insulin secretion and suppresses glucagon secretion during hyperglycemia in a glucose-dependent manner. It also protects beta cells from oxidative and toxic injury and promotes expansion of beta cell mass. Advantages: Clinical data have revealed that GLP-1 analog drugs are as effective as insulin in improving glycemic control while reducing body weight in people suffering from type 2 DM. Furthermore, the incidence of hypoglycemia is low with these drugs because of their glucose-dependent mechanism of action. Another significant advantage of these drugs is their duration of action. While insulin injections are administered at least once daily, long-acting GLP-1 analogs have been developed as once-a-week injections and could potentially be administered even less frequently than that in diabetic cats. Outline: This article reviews the physiology of incretin hormones, and the pharmacology and use of GLP-1 analogs, with emphasis on recent research in cats. Further therapies that are based on incretin hormones, such as DPP-4 inhibitors, are also briefly discussed, as are some other treatment modalities that are currently under investigation.