Cardiovascular Outcomes of Tirzepatide Compared with Glucagon-Like Peptide-1 Receptor Agonist (GLP-1) and Insulin in Patients with Type-2 Diabetes: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Cardiovascular disease remains a major cause of morbidity and mortality among patients with type 2 diabetes mellitus, highlighting the need for antidiabetic therapies that provide metabolic benefits without increasing cardiovascular risk. This study aimed to evaluate the cardiovascular outcomes of tirzepatide compared with glucagon-like peptide-1 receptor agonists (GLP-1 RAs), insulin therapy, and placebo in adults with type 2 diabetes mellitus. A systematic review and meta-analysis was conducted in accordance with the PRISMA guidelines. PubMed, Scopus, CENTRAL, and ScienceDirect databases were searched from inception to April 2026. Seven randomized controlled trials involving 21,108 participants met the eligibility criteria. Risk ratios (RRs) with 95% confidence intervals (CIs) were calculated using the Mantel–Haenszel method, and subgroup analyses were performed according to comparator class. Tirzepatide did not significantly alter the risk of myocardial infarction compared with pooled comparators (RR 1.97; 95% CI 0.52–7.43; p = 0.31) or stroke (RR 2.47; 95% CI 0.45–13.52; p = 0.30). The risk of all-cause mortality was also comparable between groups (RR 1.05; 95% CI 0.38–2.89; p = 0.92). Comparator-based subgroup analyses yielded similarly nonsignificant results. In conclusion, tirzepatide demonstrated a cardiovascular safety profile comparable to GLP-1 receptor agonists, insulin therapy, and placebo; however, additional long-term studies are required to determine whether it provides superior cardiovascular benefits.