Abstract 15406: Sitagliptin Shows No Significant Benefit on Cardiac Outcomes: Systematic Review and Meta-Analysis
Background: The use of antidiabetic medications has been linked to both increases and decreases in cardiac outcomes, depending on the class of medication or even the specific agent used. We conducted a meta-analysis of existing data from randomized controlled trials (RCTs) evaluating the effect of sitagliptin, a dipeptidyl peptidase 4 inhibitor, on the cardiovascular outcomes of unstable angina (UA), myocardial infarction (MI), congestive heart failure (CHF), and coronary artery disease (CAD) in patients with type 2 diabetes (T2DM).
Methods: A systematic literature search was conducted using PubMed, Embase, and Cochrane Central through 02/2014 without any language restrictions. Two investigators were responsible for study selection and data extraction, with any discrepancies resolved through discussion. A random effects meta-analysis yielded relative risk (RR) and 95% confidence interval (CI) for UA, MI, CHF, and CAD.
Results: A total of 10 RCTs (n=4371 patients, mean age range: 49 to 69 years, range: 12 to 54 weeks duration, mean BMI range: 25 to 34 kg/m2 and mean A1C range: 5.4 to 9.9%. Trials evaluated sitagliptin versus placebo either as monotherapy or in addition to a background regimen of metformin (UA: n=4 studies, MI: n=9 studies, CHF: n=3 studies and CAD: n=5 studies). Meta-analysis found that there was no significant effect of sitagliptin compared to placebo on any of these cardiac outcomes: UA RR 0.70 (95%CI 0.03 to 17.90), MI RR 0.82 (95%CI 0.18 to 3.51), CHF RR 2.07 (95%CI 0.05 to 84.32), CAD RR 0.71 (95%CI 0.18 to 2.75). No heterogeneity was detected in any of these analyses.
Conclusion: These are outcomes that require careful attention in future studies, as the cardiovascular risk associated with the use of sitagliptin cannot be ruled out. The event rates observed in RCTs are quite low, limiting the precision of the results. Additionally, RCTs may not be of sufficient duration to detect and report these outcomes in patients with T2DM. Future analyses of how sitagliptin works in real-world observational settings should be conducted.
Author Disclosures: R.V. Yin: None. D. Tang: None. C. Patel: None. J. Yoon: None. P. Sidhu: None. O.J. Phung: None.
- © 2014 by American Heart Association, Inc.