Meta-analysis of dipeptidyl peptidase-4 inhibitors use and cardiovascular risk in patients with type 2 diabetes mellitus.
OBJECTIVE
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.
Department of Clinical Medicine (Pharmaceutical Medicine), Kitasato University Graduate School of Pharmaceutical Sciences, 5-9-1 Shirokane, Minato-ku, Tokyo 108-8641, Japan. Electronic address: kanekom@pharm.kitasato-u.ac.jp.
Masayuki
M
Kaneko
Department of Clinical Medicine (Pharmaceutical Medicine), Kitasato University Graduate School of Pharmaceutical Sciences, 5-9-1 Shirokane, Minato-ku, Tokyo 108-8641, Japan. Electronic address: narukawam@pharm.kitasato-u.ac.jp.
Mamoru
M
Narukawa
D002318:Cardiovascular Diseases / Q000139:chemically induced* / Q000188:drug therapy; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000009:adverse effects* / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D012307:Risk Factors; D016896:Treatment Outcome
D054873:Dipeptidyl-Peptidase IV Inhibitors; D007004:Hypoglycemic Agents
Cardiovascular risk; Dipeptidyl peptidase-4 inhibitors; Meta-analysis; Type 2 diabetes mellitus