Dipeptidyl peptidase-4 (DPP-4) inhibitors may increase the risk of hospital admission for heart failure in type 2 diabetes patients with existing cardiovascular conditions or multiple vascular risk factors, according to a study published in BMJ.

However, the general effect of DPP-4 inhibitors on the risk of heart failure in patients with type 2 diabetes (without existing cardiovascular conditions or additional risk factors) cannot be determined due to low-quality evidence and short follow-up periods.

The meta-analysis included 43 trials and 12 observational studies with a total of 68,775 participants. To assess the quality of evidence in these studies, researchers used the grading of recommendations assessment, development, and evaluation (GRADE) methodology.

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The only evidence that was of moderate quality came from randomized controlled trials that looked at how DPP-4 inhibitors affected hospital admissions for heart failure. Of the 37,028 patients included in 3 large studies, 1,174 events of admission for heart failure were recorded (3.4% event rate for DPP-4 inhibitors versus 3.0% for controls).

There were 38 trials that reported heart failure for a total of 75 events among 28,292 patients treated with at least one medication. Overall, the data showed no significant difference between rates of heart failure in those treated with DPP-4 inhibitors versus those treated with control. However, the quality of evidence was low due to risk of bias and imprecision.

The evidence from the 12 observational studies was determined to be of very low quality, and thus the researchers were unable to draw any conclusions from that data.

“With respect to the incidence of heart failure, trial evidence leaves uncertainty regarding the relative effect of DPP-4 inhibitors,” the researchers wrote. “Because the follow-up was relatively short and the baseline risk of patients was very low in those trials, the incidence of heart failure was very low (well under 1% per year), and with the small number of events, the confidence intervals around relative effects are wide.”


  1. Li L, Li S, Deng K, et al. Dipeptidyl peptidase-4 inhibitors and risk of heart failure in type 2 diabetes: systematic review and meta-analysis of randomised and observational studies. BMJ. 2016;352:i610.