Can a dual incretin-based therapy offer cardiovascular benefit beyond established glucagon-like peptide-1 receptor agonists in high-risk type 2 diabetes? An indirect comparison suggests that tirzepatide may be associated with lower cardiovascular event rates and mortality in individuals with established atherosclerotic cardiovascular disease, according to findings published in Diabetes Care.

This prespecified exploratory analysis combined data from the SURPASS-CVOT trial and the REWIND trial. The dataset included all 13,165 participants from SURPASS-CVOT and 2,055 individuals from REWIND who met similar eligibility criteria. Propensity score methods were applied to address differences in baseline characteristics across the two study populations. The treatment effect of tirzepatide versus placebo was estimated indirectly by integrating the hazard ratio (HR) for tirzepatide versus dulaglutide from SURPASS-CVOT with the HR for dulaglutide versus placebo from REWIND. Sensitivity analyses were conducted using unadjusted models, the full REWIND cohort, and additional data from a glucagon-like peptide-1 receptor agonist meta-analysis.

The analysis showed lower risk of MACE-3 (HR 0.72; 95% CI 0.55-0.94), cardiovascular death or heart failure events (HR 0.70; 95% CI 0.51-0.96), and all-cause mortality (HR 0.61; 95% CI 0.45-0.82) with tirzepatide versus placebo. Results remained directionally consistent across sensitivity analyses.

These findings indicate that tirzepatide may be associated with improved cardiovascular outcomes, although interpretation should consider the indirect nature of the comparison.