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Does dipeptidyl peptidase IV inhibitor increase the risk of heart failure? A cardiologist’s paradox

Kanakia, Rushita; Martinho, Shaunc; Patel, Tejasa; Arain, Faisal A.a; Panday, Manoj M.b; Le Saux, Claude J.b; Pham, Son V.b; Bailey, Steven R.a; Chilton, Roberta

doi: 10.1097/XCE.0000000000000036

Diabetes patients have a higher burden of cardiovascular disease compared with the general population. In addition, type 2 diabetes portends a very high risk for major adverse cardiovascular events. The SAVOR trial showed that patients with documented type 2 diabetes and a previous history of, or risk factors for, cardiovascular disease had a 1-year cardiovascular event rate of 2–3%. Whereas in the EXAMINE trial, type 2 diabetes patients with acute coronary syndrome had a 1-year event rate between 6 and 7% after revascularization. Both of these prospective trials used new dipeptidyl peptidase IV (DPP-4) inhibitors as the treatment modality. Clinically, this class of compounds is extremely well tolerated by patients. The new DPP-4 inhibitors were promising from previous meta-analyses at reducing cardiovascular outcomes. In this article, we review literature on the cardiovascular outcomes with oral hypoglycemic agents, focusing on the two recent, large prospective trials on DDP-4 inhibitors. It is important to recognize that these trials enrolled different patients. The SAVOR trial had type 2 diabetes patients (>40 years old) with established cardiovascular disease or multiple cardiovascular risk factors, whereas EXAMINE trial had type 2 diabetes patients (>18 years old) 15–90 days postrevascularization for acute coronary syndrome. The primary cardiovascular endpoint was a composite of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke. Neither trial showed a significant cardiovascular benefit. However, neither trial showed increased cardiovascular mortality.

aDivision of Cardiology, The University of Texas Health Science Center at San Antonio

bDivision of Cardiology, Audie L Murphy VA

cDivision of Cardiology, San Antonio Military Medical Center, Fort Sam Houston, San Antonio, Texas, USA

Correspondence to Robert Chilton, DO, FACC, 7400 Merton Minter, San Antonio, Texas 78229, USA Tel: +210 567 4601; e-mail:

Received April 29, 2014

Accepted May 14, 2014

Copyright © 2014 Wolters Kluwer Health, Inc. All rights reserved.