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

Study Questions:

What is the cardiovascular (CV) safety of dipeptidyl peptidase-4 (DPP4) inhibitors, a novel class of oral diabetic medications?


The authors performed a meta-analysis of DPP4 inhibitors for type 2 diabetes mellitus (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 A search of electronic databases of published and unpublished literature (until September 30, 2011) was performed to identify randomized controlled trials of 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 their 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 relative risk (RR) of any adverse CV event with a DPP4 inhibitor was 0.48 (0.31-0.75, p = 0.001), and the RR for nonfatal myocardial infarction or acute coronary syndrome was 0.40 (0.18-0.88, p = 0.02).


The authors concluded that this meta-analysis provides evidence that DPP4 inhibitors are safe from a CV standpoint, and may possibly decrease risk of adverse CV events.


The present meta-analysis suggests that DPP4 inhibitors as a class appear to decrease the risk of CV events during long-term treatment. In contrast, multiple drugs for type 2 DM including sulfonylureas, insulin, and rosiglitazone have been associated with increased risk of CV events. This analysis could not determine whether the difference between CV outcomes was due to decreased risks with DPP4 inhibitors or increased risks with active type 2 DM comparators (sulfonylureas, thiazolidinediones, metformin, etc.), and adequately powered randomized trials are indicated to resolve these issues.

Clinical Topics: Acute Coronary Syndromes, Heart Failure and Cardiomyopathies, ACS and Cardiac Biomarkers, Heart Failure and Cardiac Biomarkers

Keywords: Myocardial Infarction, Insulin, Acute Coronary Syndrome, Dipeptidyl Peptidase 4, Transcription Factors, Risk Factors, Dipeptidyl-Peptidase IV Inhibitors, Sulfonylurea Compounds, Metformin, Cardiology, Cardiovascular Diseases, Hypoglycemic Agents, Thiazolidinediones, Diabetes Mellitus

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