Diabetes Mellitus: Dipeptidyl Peptidase 4 Inhibitors and Cardiovascular Outcomes

Abstract

Dipeptidyl peptidase 4 (DPP‑4) inhibitors represent a new pharmacological class of glucose – lowering agents, mainly used as add-on therapy, after metformin or combination of metformin with sulfonylurea or metformin with a thiazolidinedione. Over the last few years, several DPP‑4 inhibitors, also called gliptins, have been approved and introduced into clinical practice such as sitagliptin, linagliptin, saxagliptin, vildagliptin and alogliptin. Their mechanism of action relates to the inhibition of the DPP-4 enzyme which degrades the incretin hormones, e.g. glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), released from the small intestine into the circulation during a meal, potentially capable to stimulate the release of insulin from pancreatic beta cells, thus affording a glucose-lowering action. However, these incretins are swiftly degraded by the DPP-4 enzyme. Gliptins, therefore, inhibit this enzyme, enhancing the bioavailability of GLP-1 and GIP. They have been approved for better glycemic control in type 2 diabetic patients.

Although, these new agents have been heralded as safe agents conferring pleiotropic or cardioprotective effects, recent studies showed that the new DPP-4 inhibitors may not have serious adverse cardiovascular effects, but have failed to show any pleiotropic actions or favorable cardiovascular effects. Additional data from ongoing studies may shed further light on this issue.