Title:Efficacy and Cardiovascular Safety of DPP-4 Inhibitors
Volume: 16
Issue: 2
Author(s): Nikhila A. Subrahmanyan, Rithika M. Koshy, Koshy Jacob and Joseph M. Pappachan*
Affiliation:
- Department of Endocrinology & Metabolism, Lancashire Teaching Hospitals NHS Foundation Trust, Preston, PR2 9HT,United Kingdom
Keywords:
Dipeptidyl peptidase-4 (DPP-4) inhibitors, gliptins, cardiovascular outcome trial (CVOT), heart failure, type 2 diabetes
mellitus (T2DM), glycated hemoglobin (HbA1).
Abstract: 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.
