Effect of Dipeptidyl Peptidase-4 Inhibitors on Heart Failure: A Network Meta-Analysis

Previous meta-analyses evaluating the effectiveness of individual dipeptidyl peptidase-4 (DPP-4) inhibitors on the risk of heart failure (HF) were limited because of the small number of trials with direct comparisons between two treatments.

A Bayesian network meta-analysis was performed to investigate the relationship between DPP-4 inhibitors and the risk of HF in patients with type-2 diabetes mellitus. The primary outcome was the occurrence of HF or hospital admission for HF.

Fifty randomized controlled trials were identified. Relative to placebo, no increased risk of HF events was seen for vildagliptin (risk ratio [RR] 0.71; 95% confidence interval [CI] 0.25-1.68), sitagliptin (RR 0.86; CI 0.43-1.57), or saxagliptin (RR 0.84; 95% CI 0.33-1.61), but alogliptin was associated with a higher risk of HF (RR 2.13; 95% CI 1.06-6.26). Vildagliptin and sitagliptin were associated with a significantly decreased risk of HF compared with alogliptin. Vildagliptin had the highest probability to be the safest option with regard to the risk of HF (49.18%), followed by saxagliptin (26.56%), sitagliptin (20.76%), linagliptin (0.25%), and alogliptin (0.12%). A statistically significant inconsistency was noted in some comparisons.

The risk of HF needs to be taken into account when prescribing DPP-4 inhibitors. Evidence suggests that vildagliptin may be the least harmful agent with regard to the risk of HF. However, a statistically significant inconsistency was identified in the Bayesian network meta-analysis. Therefore, further studies are warranted to evaluate the cardiovascular safety of DPP-4 inhibitors.