AHA Scientific Sessions 2026 Abstract · Nov 2, 2026
Trajectory of Predicted 10-year Cardiovascular Disease Risk with Tirzepatide Dose Modifications: A Post-Hoc Analysis from the SURMOUNT-MAINTAIN Trial
By Honigberg M, Lewis K, Mamas M et al.
Introduction: SURMOUNT-MAINTAIN, a 112-week trial, evaluated once-weekly tirzepatide (TZP) maximum tolerated dose (MTD) and TZP dose modifications in adults with a BMI ≥30 kg/m ² or ≥27 kg/m ² with at least one weight-related comorbidity, and without diabetes. This post-hoc analysis assessed the relationship of continued TZP MTD, TZP reduced to 5 mg, or TZP switched to placebo with the trajectory of CM risk factors and, subsequently, predicted cardiovascular disease (CVD) risk among participants without baseline CVD. Research Question: To evaluate how A) continued TZP MTD, B) TZP reduced to 5 mg, or C) TZP switched to placebo were associated with changes in predicted 10-year CVD risk in adults with obesity or overweight, without diabetes or established CVD at baseline. Methods: After 60 weeks of TZP MTD (10 mg or 15 mg), participants were randomized in a 3:3:2 ratio to continue TZP MTD, reduce to TZP 5 mg, or switch to placebo in a 52-week double blind Weight Maintenance Period (Week 60-112). Rescue TZP was allowed starting Week 84 for participants with 50% or more weight regain of the initial weight reduction achieved during Weeks 0 to 60. This post-hoc analysis evaluated predicted 10-year CVD risk from baseline (Week 0) to Week 112 among participants without established CVD at baseline. 10-year CVD risk was calculated using BMI-based Framingham CVD risk equations and contemporaneous risk factor values at every visit. Hazard Ratio (HR) was estimated using the ratio of the negative logarithms of the group level predicted 10-year survival. Results: A total of 359 participants had no preexisting CVD at baseline, and 133, 138, and 88 participants were randomized to MTD, 5 mg, and placebo, respectively. Average predicted 10-year CVD risk at baseline was 10.3% (standard deviation 9.73%). After 112 weeks, TZP MTD was associated with a significant reduction in predicted 10-year CVD risk when compared to switching to placebo (difference vs placebo -2.4% [95% confidence interval (CI) -3.4 to -1.4]; p<0.001) [Figure 1]. TZP 5 mg also demonstrated a significant reduction vs placebo (difference vs placebo -1.3% [95% CI -2.3 to -0.3]; p=0.01). The estimated HR vs placebo was 0.77 (95% CI: 0.69-0.85) for TZP MTD and 0.87 (95% CI: 0.79-0.97) for TZP 5 mg [Figure 1]. Conclusions: In this post-hoc analysis, continuation of TZP MTD was associated with the greatest reduction in predicted 10-year CVD risk, while reduction of TZP to 5 mg was also associated with CVD risk reduction compared with switching to placebo. These findings support the potential cardiovascular benefits of continued TZP treatment, with greater benefit observed at MTD, and suggest a role for TZP in primary CVD prevention in adults with obesity.