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Preferred GLP-1 Receptor Agonists in Type 2 Diabetes With Established Cardiovascular Disease or High Cardiovascular Risk: A Network Meta-Analysis of Randomized Trials.
Can J Diabetes · 2026
Last updated 2026-05-28A review of 11 clinical trials involving 83,215 people with type 2 diabetes and high heart disease risk found that several GLP-1 drugs lowered the chance of major heart-related events compared to a placebo. Subcutaneous semaglutide, efpeglenatide, and albiglutide showed the strongest effects, while tirzepatide, oral semaglutide, liraglutide, and dulaglutide also performed better than placebo. No drug significantly reduced overall or heart-related deaths, and some drugs had higher rates of side effects leading to stopping treatment.
AI summary of the abstract below.
| Journal | Can J Diabetes, 2026 |
|---|---|
| Citations | 0 |
| Molecules | — |
| Conditions studied | Type 2 Diabetes, Cardiovascular Risk Reduction |
Abstract
BACKGROUND: The comparative cardiovascular (CV) efficacy and safety of GLP-1 receptor agonists (GLP-1RAs) in patients with type 2 diabetes (T2D) and established cardiovascular disease (CVD) or high CV risk remain uncertain.
METHODS: PubMed, Embase, Web of Science, Scopus, and CENTRAL were searched from inception to 20 December 2025 for randomized controlled trials. We conducted a frequentist random-effects network meta-analysis and reported risk ratios (RRs) with 95% confidence intervals (CIs). Treatments were ranked using P-scores. Regimens were analyzed as individual agents, including albiglutide, dulaglutide, efpeglenatide, exenatide ER, ITCA 650, liraglutide, lixisenatide, subcutaneous semaglutide, oral semaglutide, tirzepatide, and placebo.
RESULTS: Eleven trials (n=83,215) were included. In the three-point major adverse CV event (MACE) network (11 trials; 11 regimens), heterogeneity and inconsistency were absent (I2=0%; τ2=0). MACE was reduced with subcutaneous semaglutide (RR 0.74, 95% CI 0.58-0.94), efpeglenatide (0.76, 0.61-0.94), and albiglutide (0.79, 0.69-0.91); tirzepatide, oral semaglutide, liraglutide, and dulaglutide were also significant compared with placebo. Top ranks were semaglutide SC (P-score 0.87), efpeglenatide (0.84), and albiglutide (0.80). No regimen significantly reduced all-cause or CV death compared with placebo. Stroke was reduced with tirzepatide (RR 0.71, 0.54-0.93) and dulaglutide (0.77, 0.63-0.95) compared with placebo. Discontinuation and gastrointestinal discontinuation were higher with subcutaneous semaglutide, oral semaglutide, lixisenatide, and ITCA 650.
CONCLUSION: Several GLP-1-based therapies reduced MACE versus placebo, with 3-point MACE emerging as the most consistent efficacy signal. Overall, these findings support guideline-based use of GLP-1 RAs in high-risk T2DM while highlighting the need for individualized treatment selection.
Verbatim abstract via PubMed 41967797 ↗