Cardiovascular Outcomes in Adults With Type 2 Diabetes Treated With Tirzepatide: A Systematic Review and Meta-Analysis of Real-World Studies.

OBJECTIVE: Tirzepatide shows benefits on cardiovascular (CV) parameters and major adverse cardiovascular events (MACE) in clinical trials, but real-world data, especially for type 2 diabetes (T2D), are limited. This systematic review and meta-analysis seeks to address this gap. METHODS: Multiple databases and registries were searched for real-world observational studies involving individuals with T2D receiving tirzepatide. The co-primary outcomes were acute coronary syndrome (ACS), heart failure (HF), sudden cardiac death, and stroke. RevMan Web was used to conduct meta-analyses employing random-effects models to calculate hazard ratios (HRs) with 95% confidence intervals (CIs). RESULTS: Eight retrospective cohort studies (N = 118 252) were included. Compared to the control group, tirzepatide reduced risks of ACS (HR 0.74 [0.62-0.89], P = .001), HF (HR 0.65 [0.53-0.82], P = .0002), stroke (HR 0.71 [0.62-0.81], P < .00001), MACE (HR 0.72 [0.60-0.86], P = .0004), and all-cause mortality (HR 0.49 [0.37-0.67], P < .00001). However, the risk of sudden cardiac death was similar between groups. The risk of composite outcomes of all-cause mortality plus CV outcomes was also lower with tirzepatide (HR 0.65 [0.54-0.79], P < .0001). Compared to semaglutide, tirzepatide had lower risks of stroke and MACE but similar risks for ACS, HF, sudden cardiac death, all-cause mortality, and composite outcomes. CONCLUSIONS: Tirzepatide offers the potential to reduce the risks of ACS, HF, stroke, MACE, and death in real-world patients with T2D, suggesting CV benefits. Larger trials are needed to confirm long-term CV effects and define its role in T2D and CV management.