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Background  Dipeptidyl peptidase 4 (DPP-4) inhibitors are newer oral anti-diabetic agents which have been approved by the Food and Drug Administration for the treatment of patients with type 2 diabetes mellitus (T2DM). In this analysis, we aimed to systematically compare the cardiovascular outcomes associated with DPP-4 inhibitors versus non-DPP-4 inhibitor users.    Methods  All English publications that compared the use of DPP-4 inhibitors and that reported cardiovascular outcomes in patients with T2DM were searched using specific terms. Studies were included if they satisfied the following inclusion criteria: They were randomized trials or observation cohorts/registries comparing DPP-4 inhibitors use in patients with T2DM; The studies included a large sample size of participants; And they reported cardiovascular outcomes as their main endpoints. RevMan 5.3 was used to analyze the data, and odds ratios (OR) with 95% confidence intervals (CI) were used to represent the results.    Results  A total number of 157,478 participants with T2DM were included. Seventy-six thousand and twenty six patients were assigned to the DPP-4 inhibitor group whereas 81,452 patients were assigned to the control group. Results of the current analysis showed that during a mean follow-up time period ranging from 52 to 152 weeks, the primary endpoint (cardiovascular death/non-fatal myocardial infarction (MI)/non-fatal stroke) was not significantly different in the treatment of T2DM patients with versus without DPP-4 inhibitors (OR: 0.95, 95% CI: 0.86–1.04;  P  = 0.26). Cardiovascular death (OR: 1.00, 95% CI: 0.90–1.10;  P  = 0.93), stroke (OR: 1.03, 95% CI: 0.89–1.18;  P  = 0.72), MI (OR: 0.97, 95% CI: 0.88–1.07;  P  = 0.59), all-cause mortality (OR: 0.84, 95% CI: 0.59–1.18;  P  = 0.31), hospitalization for cardiovascular complications (OR: 1.02, 95% CI: 0.96–1.09;  P  = 0.45) and hospitalization specifically for heart failure (OR: 1.05, 95% CI: 0.90–1.23;  P  = 0.55) were also similarly manifested in both groups.    Conclusion  The current analysis showed that treatment with DPP-4 inhibitors did not significantly increase cardiovascular outcomes in these patients with T2DM indicating that those drugs might be safe to use in terms of cardiovascular events.

bmc pharmacology and toxicology

Dipeptidyl peptidase 4 (DPP-4) inhibitors and cardiovascular outcomes in patients with type 2 diabetes mellitus (T2DM): a systematic review and meta-analysis