Tirzepatide versus dulaglutide in type 2 diabetes: a comparative meta-analysis of cardiometabolic outcomes and safety

Background Incretin-based therapies are central to type 2 diabetes (T2D) management, and glucagon-like peptide-1 receptor agonists improve glycaemic control and reduce cardiovascular risk. Dulaglutide has demonstrated cardiovascular benefit, making it a clinically relevant active comparator. Tirzepatide, a dual glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonist, shows greater metabolic efficacy in head-to-head trials, but its comparative cardiometabolic and safety profile versus dulaglutide has not been fully synthesised. Purpose To compare cardiometabolic effects, cardiovascular outcomes, and safety of tirzepatide versus dulaglutide in adults with T2D. Methods PubMed and Embase were searched through 15 February 2026 for randomised controlled trials (RCTs) comparing tirzepatide with dulaglutide in patients with type 2 diabetes. Random-effects models pooled mean differences (MD) with 95% confidence intervals (CI). Effect estimates were derived from placebo-adjusted least-squares mean (LSM) changes and corresponding standard errors. Exploratory analyses assessed effects by follow-up duration. Heterogeneity was assessed using the Chi-squared test and I² statistic. Results Three RCTs, including 14,066 patients (7,274 in tirzepatide group and 6,792 in dulaglutide groups), were analysed. Tirzepatide reduced HbA1c (MD -1.13; CI -1.83 to -0.42), bodyweight (MD -8.46 kg; CI -11.79 to -5.13) and triglycerides (MD -21.34 mg/dL; CI -36.50 to -6.17) versus dulaglutide. Systolic blood pressure was numerically lower but not significant (MD -5.73 mmHg; CI -13.07 to 1.62). Low-density lipoprotein cholesterol effects were not significant overall and varied by follow-up duration. In analyses of major cardiovascular outcomes, no significant differences in myocardial infarction (RR 0.87; CI 0.75 to 1.01) or stroke (RR 0.92; CI 0.77 to 1.10) were found between groups. All-cause mortality was lower with tirzepatide (RR 0.85; CI 0.76 to 0.94), driven by the cardiovascular outcomes trial. Adverse events leading to treatment discontinuation were more frequent with tirzepatide (RR 1.31; CI 1.19 to 1.43). Conclusion(s) In adults with T2D, tirzepatide produced greater improvements in HbA1c, bodyweight and triglycerides than dulaglutide, while effects on systolic blood pressure and low-density lipoprotein cholesterol were not significant overall and appeared time-dependent. Myocardial infarction and stroke were not significantly different between groups. All-cause mortality was lower with tirzepatide, driven by the cardiovascular outcomes trial, whereas smaller short-term trials contributed no mortality events. Higher discontinuation due to adverse events underscores the need to balance metabolic benefit against tolerability and to refine long-term clinical outcome estimates with continued follow-up.