Meta-Analysis of Effect of Dipeptidyl Peptidase-4 Inhibitors on Cardiovascular Risk in Type 2 Diabetes Mellitus

Harshal R. Patil, Firas J. Al Badarin, Hamza A. Al Shami, Salman K. Bhatti, Carl J. Lavie, David S.H. Bell, James H. O'Keefe

Patients with type 2 diabetes mellitus (DM) have a very high risk for major adverse cardiovascular (CV) events. Previous studies have shown that traditional oral diabetic medications, despite lowering blood glucose levels, generally do not improve CV outcomes. The safety of some oral hypoglycemic medications has been questioned. We aimed to evaluate the CV safety of dipeptidyl peptidase-4 (DPP4) inhibitors, a novel class of oral diabetic medications, by performing a meta-analysis of DPP4 inhibitors for type 2 DM. A search of electronic databases of published and unpublished literature (until September 30, 2011) was performed to identify randomized controlled trials of ≥24 weeks that compared DPP4 inhibitors to other oral diabetic medications. A meta-analysis was performed using fixed and random effects to determine risk ratio (RR) for adverse CV events with DPP4 inhibitor monotherapy compared to other oral diabetic medications or to placebo. Eighteen randomized met our inclusion criteria, comprising 4,998 patients who were randomized to DPP4 inhibitors and 3,546 to a comparator, with a median duration of therapy of 46.4 weeks. In pooled analysis, the RR of any adverse CV event with a DPP4 inhibitor was 0.48 (0.31 to 0.75, p = 0.001), and the RR for nonfatal myocardial infarction or acute coronary syndrome was 0.40 (0.18 to 0.88, p = 0.02). In conclusion, this meta-analysis provides evidence that DPP4 inhibitors are safe from a CV standpoint and may possibly decrease risk of adverse CV events.