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

Rushit Kanakia, Shaun Martinho, Tejas Patel, Faisal A. Arain, Manoj M. Panday, Claude J. Le Saux, Son V. Pham, Steven R Bailey, Robert Chilton

Research output: Contribution to journalReview articlepeer-review

1 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)111-116
Number of pages6
JournalCardiovascular Endocrinology
Issue number4
StatePublished - Dec 1 2014


  • Cardiovascular outcomes
  • Diastolic dysfunction
  • Dipeptidyl peptidase IV inhibitors
  • Heart failure

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Endocrine and Autonomic Systems
  • Cardiology and Cardiovascular Medicine


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