Efficacy and Cardiovascular Safety of DPP-4 Inhibitors

Dipeptidyl peptidase-4 (DPP-4) inhibitors or gliptins belong to the class of incretin mimetics. These drugs have been available on the market for the management of type 2 diabetes mellitus (T2DM) for over a decade. Sitagliptin, linagliptin, vildagliptin, saxagliptin and alogliptin are widely available globally, whilst anagliptin, gemigliptin and teneliptin are used mainly in the Asian countries. The glycemic control conferred by DPP-4 inhibitors varies among individual molecules with an average reduction of glycated hemoglobin (HbA1c) ranging between -0.5 to -1.0% with monotherapy. Additive effects on HbA1c reduction may result from combination therapy with other antidiabetics. Weak evidence from various studies suggests that DPP-4 inhibitors may be useful in treating nonalcoholic fatty liver disease (NAFLD) and polycystic ovary syndrome (PCOS). DPP-4 inhibitors safety is not established in pregnancy, and there is only meagre evidence of its use in T2DM among children. In line with the United States Food and Drug Administration (US FDA) recommendations, sitagliptin, linagliptin, saxagliptin and alogliptin have undergone rigorous cardiovascular outcome trials (CVOTs) in recent years, and the safety data for vildagliptin is available through retrospective analysis of various studies in meta-analysis. Small clinical trial, and meta-analysis based data are available for the CV safety of other DPP-4 inhibitors. In general, the CVOTs and other safety data do not reveal serious warning signals except for saxagliptin (higher risk of hospitalization from heart failure [hHF]), although there is no robust data on the risk of hHF among patients with moderate to severe HF at baseline treated with other DPP-4 inhibitors. This review critically appraises the efficacy and cardiovascular safety of DPP-4 inhibitors to empower clinicians to use this class of antidiabetic medications judiciously.