The cardiovascular effect of incretin-based therapies among type 2 diabetes: a systematic review and network meta-analysis

ABSTRACT

Objective: To evaluate the comparative cardiovascular safety of incretin-based therapies in patients with type 2 diabetes mellitus (T2DM).

Methods: Medline, Embase, the Cochrane Library and www.clinicaltrials.gov were searched for randomized controlled trials (RCTs) with duration≥12 weeks. Network meta-analysis was performed, followed by subgroup analysis and meta-regression. The Grading of Recommendations Assessment, Development and Evaluation system was used to assess the quality of evidence. The outcome of interest was a composite of cardiovascular death, myocardial infarction, stroke and heart failure. Odds ratio (OR) with 95% confidence interval (CI) was calculated as the measure of effect size.

Results: 281 RCTs (76.9% double-blinded) with 180,000 patients were included, comparing incretin-based therapies with other six classes of anti-diabetic drugs or placebo. A statistically significant reduction in the risk of cardiovascular events was found in favour of GLP-1RAs when compared with placebo (OR 0.89, 95%CI: 0.80–0.99) and sulfonylurea (OR 0.76, 95%CI: 0.59–0.99), whereas DPP-4 inhibitors showed a neutral effect compared with placebo (OR 0.92, 95%CI: 0.83–1.01).

Conclusions: Incretin-based therapies show similar cardiovascular risk in comparison with metformin, insulin, thiazolidinediones, alpha-glucosidase inhibitor and sodium-glucose co-transporter 2. GLP-1RA could decrease the risk compared with sulfonylurea or placebo, while DPP-4I appears to have neutral effect on cardiovascular risk.

KEYWORDS:

• Incretin-based therapies
• type 2 diabetes
• network meta-analysis
• cardiovascular effect

Acknowledgments

We are grateful to all cooperating organizations and their staff whose hard work made this study possible. AC is supported by the NIHR Oxford Cognitive Health Clinical Research Facility. ZRY is supported by the Cambridge Trust and the China Scholarship Council.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties. Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

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Funding

This study is funded by National Natural Science Foundation of China (81302508, 71673003). The sponsor had no role in study design, data collection, data analysis, data interpretation, or writing of the report.