Cardiovascular and Cerebrovascular Outcomes Risk Reduction Associated With Semaglutide vs Tirzepatide

Figure 1. Target Trial Emulation Flow Diagram BMI = body mass index; CV = cardiovascular; GLP-1 = glucagon-like peptide-1; PAD = peripheral artery disease; TIA = transient ischemic attack.

Figure 2. Comparative Risk Ratio for All Outcomes Forest Plot MI = myocardial infarction; RR = risk ratio; other abbreviations as in Figure 1.

Figure 3. Cumulative Incidence of Heart Failure Curve

Figure 4. Comparative Outcomes at 1-Year Follow-up Interval Plot Abbreviations as in Figures 1 and 2.

Figure 5. Effect Modification by Diabetes Status Plot Abbreviations as in Figures 1 and 2.

Figure 6. Additive Interaction Effects Across Outcomes Plot Abbreviation as in Figure 1.

Figure 7. Time-Evolution of Treatment Effects Plot Abbreviations as in Figures 1 and 2.

Central Illustration. Tirzepatide vs Semaglutide: Cardiovascular and Cerebrovascular Risk Reduction Central Illustration summarizing the comparative effectiveness of tirzepatide vs semaglutide for cardiovascular and cerebrovascular risk reduction across 217,920 propensity score–matched adults (48,507 type 2 diabetes pairs; 60,453 nondiabetic pairs) followed for 1 and 3 years. Across all 6 evaluated endpoints—heart failure, atrial fibrillation, acute myocardial infarction, ischemic stroke or transient ischemic attack, peripheral artery disease, and hemorrhagic stroke—tirzepatide was associated with lower event risk compared with semaglutide, with risk ratios ranging from 0.45 to 0.88 across diabetes strata and follow-up intervals. Significant effect modification by diabetes status was observed: diabetic patients (T2D) derived greater absolute benefit owing to higher baseline cardiovascular risk, whereas nondiabetic patients (ND) experienced larger relative risk reductions. Treatment effects appeared to amplify between 1- and 3-year follow-up, suggesting progressive cardiovascular protection with sustained therapy. ND = nondiabetic; RR = risk ratio (Tirze/Sema); T2D = type 2 diabetes.