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Emerging dipeptidyl peptidase-4 inhibitors for the treatment of diabetes

Bo Ahrén
Expert Opinion on Emerging Drugs 2008, 13 (4): 593-607
19046129
Inhibition of dipeptidyl peptidase-4 (DPP-4) prevents the inactivation of glucagon-like peptide-1 (GLP-1). This increases circulating levels of active GLP-1, stimulates insulin secretion and inhibits glucagon secretion, resulting in lowering of glucose levels and improvement of glycemic control in patients with type 2 diabetes. Several DPP-4 inhibitors are emerging for therapeutic use. Most experience exists for sitagliptin, vildagliptin, saxagliptin and alogliptin. They all improve metabolic control in type 2 diabetes in monotherapy and in combination therapy with metformin, sulfonylurea and thiazolidinediones. Vildagliptin and alogliptin have also been shown to improve glycemic control when added to insulin therapy, and sitagliptin improves glycemic control in triple therapy with metformin plus thiazolidinedione. DPP-4 inhibition also shows a favorable safety profile, high tolerability, only a minimal risk of hypoglycemia, and body-weight neutrality. The main clinical indication for DPP-4 inhibitors will be in the early stage of type 2 diabetes, in combination with metformin or other treatments in subjects with inadequate glycemic control on these treatments alone. The durability and long-term safety of DPP-4 inhibition, as well as clinical positioning in relation to GLP-1 mimetics, remain now to be established.

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