Meta-analysis of dipeptidyl peptidase-4 inhibitors use and cardiovascular risk in patients with type 2 diabetes mellitus

Aims: Some meta-analyses have shown that dipeptidyl peptidase-4 (DPP-4) inhibitors decrease the risk of major adverse cardiovascular events (MACE) compared to placebo. However, this association has not been confirmed in large placebo-controlled clinical trials with cardiovascular events as a primary endpoint. The aim of the present meta-analysis is to assess the association between DPP-4 inhibitors use and cardiovascular risk using uniform definition of MACE. Methods: Relevant studies through 31 December 2014 were searched in the electronic databases, and we identified all eligible trials comparing DPP-4 inhibitors with active drugs or placebo. Summary odds ratio (OR) with 95% confidence interval (CI) for MACE was calculated using random-effects model. Results: In 69 trials included in our study, 36,488 patients were treated with DPP-4 inhibitors and 31,290 with other comparators. Treatment with DPP-4 inhibitors was associated with a lower risk of MACE (OR [95% CI] = 0.52 [0.36,0.76]) compared to sulfonylureas, while showed a trend toward increased risk (OR [95% CI] = 1.89 [0.60,5.93]) compared to sodium-glucose cotransporter 2 (SGLT2) inhibitors. The difference was not statistically significant when compared to placebo (OR [95% CI] = 1.04 [0.92,1.18]), and this tendency was similar in both subgroup analyses conducted with a general type 2 diabetes population as well as the population at high cardiovascular risk. Conclusions: There is no significant difference in the risk of MACE between DPP-4 inhibitors and placebo groups. DPP-4 inhibitors show significantly lower risk of MACE when compared to sulfonylureas, while SGLT2 inhibitors might have lower risk compared to DPP-4 inhibitors. (C) 2016 Elsevier Ireland Ltd. All rights reserved.