The effect of dipeptidyl peptidase-4 (DPP-4) inhibitors on the risk of heart failure in patients with type 2 diabetes is uncertain, based on low quality of evidence found in a systematic review and meta-analysis published in BMJ

Researchers searched Medline, Embase, Cochrane Central Register of Controlled Trials, (up to June 25, 2015), and communicated with experts to study the association between DPP-4 inhibitors and the risk of heart failure or hospitalization for heart failure in patients with type 2 diabetes. Studies that compared DPP-4 inhibitors vs. placebo, lifestyle modification, or active antidiabetic therapies in adults with type 2 diabetes were included for analysis. Data collected from trials and observational studies were pooled separately, and the quality of evidence was assessed by the GRADE approach. 

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Forty-three trials (n=68,775) and 12 observational studies (n=1,777,358) were considered eligible. Pooled data of 38 trials reporting heart failure demonstrated low quality evidence for a possible similar risk of heart failure between DPP-4 inhibitor use vs. control (odds ratio [OR] 0.97, 95% CI: 0.61-1.56); difference in risk showed 2 less events per 1,000 patients with type 2 diabetes over 5 years. 

Data from the observational studies showed estimates generally similar with trial findings but with very low quality evidence. Pooled data from the 5 studies reporting admission for heart failure offered moderate quality evidence for an increased risk in patients treated with DPP-4 inhibitors vs. control (622/18,544 vs. 552/18,474; OR 1.13, 95% CI: 1.00–1.26). Similarly, adjusted estimates from observational studies showed a possible increased risk of admission for heart failure (adjusted OR 1.41, 95% CI: 0.95-2.09) for patients treated with DPP-4 inhibitors (exclusively sitagliptin) vs. no use; this evidence was deemed very low quality.

Overall, the relative effect of DPP-4 inhibitors on heart failure risk in patients with type 2 diabetes is uncertain with the short follow-up and low quality of evidence. However, study findings suggest that these drugs may increase risk of hospital admission for heart failure in patients with pre-existing cardiovascular disease or risk factors for vascular diseases vs. no use. 

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