Via practica 7-8/2008

INCRETIN-BASED THERAPY IN THE TREATMENT OF TYPE 2 DIABETES MELLITUS

Under physiological conditions food intake stimulates incretin secretion from the gastrointestinal tract. Glucagone-like peptid 1 (GLP-1)and glucose-dependent insulinotropic polypeptide (GIP) are the most important incretins. Incretin effect is reduced in patients with type 2 diabetes mellitus. Biological half time of native GLP-1 is very short (1 – 2 minutes). GLP-1 is promptly degraded by the enzyme dipeptidyl peptidase-4 (DPP-4). There are two approaches how to eliminate prompt degradation of GLP-1. GLP-1 analogs (exenatide, liraglutide) are not degraded by DPP-4, they are used subcutaneously. Besides the stimulation of postprandial insulin secretion these drugs supress also inappropriate glucagon secretion, delay gastric emptying, and reduce food intake. In addition to increased glycemic control (HbA1c reduction approximately 0,8 – 1,0 %), GLP-1 analogs lead to reduction of body weight. DPP-4 inhibitors (sitagliptin, vildagliptin, saxagliptin, alogliptin) could be given orally. Their effect on glycemic control is similar to GLP-1 analogs, but no body weight reduction was observed. Regarding glucose-dependent stimulation of insulin seceretion, GLP-1 analogs and also DPP-4 inhibitors do not cause hypoglycemias. Incretin-based therapy represent a new therapeutic approach in the treatment of type 2 diabetes mellitus.

Keywords: type 2 diabetes mellitus, incretin-based therapy, DPP-4 inhibitors, GLP-1 analogs.