Do “Gliptin” Drugs Raise Risk for Heart Failure?

Summary and Comment |
April 9, 2015

Do “Gliptin” Drugs Raise Risk for Heart Failure?

  1. Bruce Soloway, MD

First hospital admission for heart failure was more likely with alogliptin than with placebo.

  1. Bruce Soloway, MD

The FDA requires evidence that new type 2 diabetes therapies do not raise cardiovascular (CV) risk. In previous placebo-controlled trials of dipeptidyl peptidase–4 (DPP-4) inhibitors, saxagliptin (Onglyza) was assessed in 16,500 patients with type 2 diabetes and CV disease or risk factors, and alogliptin (Nesina) was assessed in 5400 diabetic patients with recent episodes of acute coronary syndrome (NEJM JW Gen Med Oct 1 2013 and N Engl J Med 2013; 369:1317 and 1327). In the saxagliptin study, major adverse CV events (i.e., CV death, myocardial infarction, and stroke) occurred with similar frequency during 2 years in the saxagliptin and placebo groups, but incidence of congestive heart failure (CHF) hospitalizations was significantly higher in the saxagliptin group. In the alogliptin trial, incidence of major CV events was similar during 1.5 years in the treatment and placebo groups, but CHF hospitalizations were not examined. Now, the authors of the alogliptin study have analyzed CHF-related outcomes.

Major adverse CV events were more common in patients with preexisting CHF than in those without, but, among all patients, risk was similar in the alogliptin and placebo groups. Composite outcomes that included CHF hospitalization also were similar in the alogliptin and placebo groups, regardless of CHF history. However, among patients without preexisting CHF, those taking alogliptin were significantly more likely to have first CHF hospitalizations (2.2% vs. 1.3%).


The smaller alogliptin study might have lacked statistical power to discern differences in CHF outcomes that emerged in the larger saxagliptin study, and both studies were relatively brief. DPP-4 inhibitors seem to have little effect on CV-related death, myocardial infarction, or stroke, but their effects on CHF require further clarification.

Editor Disclosures at Time of Publication

  • Disclosures for Bruce Soloway, MD at time of publication Nothing to disclose


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