Real-World Evidence Supports Similar Cardiovascular Benefits of Tirzepatide and Semaglutide
Despite promising results from clinical trials, determining the optimal choice between tirzepatide and semaglutide for patients with cardiovascular risk remains challenging due to a lack of direct comparative data. To address this gap, researchers analyzed data from five large cohort studies encompassing individuals with elevated cardiovascular risk – including obesity and type 2 diabetes – enrolled in U.S. insurance programs between 2018 and 2025.
The study employed a multi-faceted approach. First, researchers recreated the designs of two key cardiovascular outcome trials – SUSTAIN-6 (semaglutide vs.sitagliptin) and SURPASS-CVOT (tirzepatide vs. dulaglutide) – to validate their methods.This “benchmarking” process showed strong alignment between the real-world data analysis and the original trial results for most outcomes, with a minor discrepancy observed in all-cause mortality within the SUSTAIN-6 emulation.
Next, the researchers evaluated the effectiveness of each drug individually in broader patient populations representative of those encountered in routine clinical practice. Semaglutide demonstrated a statistically significant reduction in the risk of myocardial infarction or stroke compared to sitagliptin (hazard ratio 0.82, 95% CI 0.74-0.91). Tirzepatide showed a trend towards reduced risk of a composite outcome including mortality compared to dulaglutide, though this did not reach statistical meaning (hazard ratio 0.87, 95% CI 0.75-1.01).
Crucially, a direct comparison of tirzepatide and semaglutide revealed no significant difference in cardiovascular outcomes (hazard ratio 1.06, 95% CI 0.95-1.18).
These findings suggest that both tirzepatide and semaglutide offer comparable cardiovascular benefits in a real-world setting. This research highlights the value of rigorously conducted observational studies in supplementing evidence from randomized controlled trials and informing clinical decision-making.
