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Cardiovascular Safety of Dipeptidyl-Peptidase IV Inhibitors: A Meta-Analysis of Placebo-Controlled Randomized Trials

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Abstract

Background

Large randomized trials have shown conflicting evidence regarding the cardiovascular safety of dipeptidyl-peptidase 4 (DPP-4) inhibitors. Systematic reviews have been limited by incomplete data and inclusion of observational studies. This study aimed to systematically evaluate the cardiovascular safety of DPP-4 inhibitors in patients with type 2 diabetes.

Methods

Electronic databases were searched for randomized trials that compared DPP-4 inhibitors versus placebo and reported cardiovascular outcomes. The main outcome assessed in this analysis was heart failure. Other outcomes included all-cause mortality, cardiovascular mortality, myocardial infarction, and ischemic stroke. Summary odds ratios (ORs) were primarily constructed using Peto’s model.

Results

A total of 90 trials with 66,730 patients were included. Compared with placebo, DPP-4 inhibitors were associated with a non-significant increased risk of heart failure [OR 1.11, 95% confidence interval (CI) 0.99–1.25, P = 0.07] at a mean of 108 weeks. The risk of all-cause mortality (OR 1.03, 95% CI 0.94–1.12, P = 0.53), cardiovascular mortality (OR 1.02, 95% CI 0.92–1.14, P = 0.72), myocardial infarction (OR 0.98, 95% CI 0.88–1.09, P = 0.69), and ischemic stroke (OR 0.99, 95% CI 0.85–1.15, P = 0.92) was similar between both groups.

Conclusion

In patients with type 2 diabetes, the safety profile of DPP-4 inhibitors is similar to placebo. As a class, there is only weak evidence for an increased risk of heart failure.

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    Authors and Affiliations

    1. Division of Cardiovascular Medicine, Department of Medicine, University of Florida, 1600 SW Archer Road, Gainesville, FL, 32610, USA

      Islam Y. Elgendy, Ahmed N. Mahmoud, Akram Y. Elgendy, Siddarth A. Wayangankar & Anthony A. Bavry

    2. Department of Medicine, Cleveland Clinic, Cleveland, OH, USA

      Amr F. Barakat

    3. Department of Medicine, University of Arkansas, Little Rock, AR, USA

      Marwan Saad

    4. Division of Cardiovascular Medicine, Jefferson University Hospital/Christiana Care Health System, Newark, DE, USA

      Ahmed Abuzaid

    5. North Florida/South Georgia Veterans Health System, Gainesville, FL, USA

      Anthony A. Bavry

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    Dr. Anthony A. Bavry discloses the following relationship: honorarium from American College of Cardiology. The other authors have no conflicts of interest to declare.

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    I. Y. Elgendy and A. N. Mahmoud equally contributed to the paper.

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    Elgendy, I.Y., Mahmoud, A.N., Barakat, A.F. et al. Cardiovascular Safety of Dipeptidyl-Peptidase IV Inhibitors: A Meta-Analysis of Placebo-Controlled Randomized Trials. Am J Cardiovasc Drugs 17, 143–155 (2017). https://doi.org/10.1007/s40256-016-0208-x

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