ESC 2025: post-hoc SURMOUNT-5 data affirms tirzepatide’s lead in CVD risk reduction (2025)

At the European Society of Cardiology (ESC) Congress 2025, findings from a post-hoc analysis of the SURMOUNT-5 trial (NCT05822830) were presented, comparing tirzepatide to semaglutide for their impact on cardiovascular disease (CVD) risk in adults with obesity but without type 2 diabetes (T2D) or established CVD. Given that reducing CVD risk is a primary objective in obesity management, the analysis aimed to estimate ten-year CVD risk reduction and project preventable primary CVD events across the US and France, Germany, Italy, Spain, and the UK (5EU).

The study utilised a BMI-based Framingham CVD risk score to evaluate ten-year CVD risk among participants who completed 72 weeks of treatment. Subgroup analyses were performed by sex, race, and baseline BMI. The projected impact of tirzepatide and semaglutide on ten-year CV events prevented was calculated by multiplying the treatment-eligible population across countries included in the study by the ten-year risk reduction estimated for each patient treated.

In results presented at the ESC conference by Professor Mamas Mamas, Keele Cardiovascular Research Group, Keele University, Stoke-on-Trent, UK, while both GLP-1 receptor agonists were associated with a reduction in ten-year CVD risk, tirzepatide achieved a significantly greater reduction in CVD risk than semaglutide (2.4% versus 1.4%, respectively; p<0.001). This trend was identified as early as 12 weeks into the study, where a clear separation can be noticed between the tirzepatide and semaglutide groups. By week 72, tirzepatide MTD (10mg or 15mg) led to a 23.7% reduction in predicted ten-year CVD risk, compared to 13.6% with semaglutide MTD (1.7mg or 2.4mg) (p<0.001). Tirzepatide consistently outperformed semaglutide across individual risk factors—including BMI, systolic blood pressure, LDL cholesterol, HbA1c, and hypertension—and demonstrated consistent benefits across demographic and BMI subgroups.

Projections based on the treatment-eligible populations suggest that tirzepatide could prevent over 3.1 million CVD events across the US and 5EU combined over ten years. In contrast, semaglutide was estimated to prevent 1.8 million across all six countries. These findings underscore tirzepatide’s potential superiority over semaglutide in primary CVD prevention among individuals with obesity without T2D, aligning with emerging real-world evidence on its cardiometabolic benefits.

Key opinion leaders (KOLs) interviewed by GlobalData expressed that “you [have] got to make sure that you show that you are not just improving the weight of the patients, but you are improving the health of the patients [too]. So, you do have to look at the diabetes, and hypertension, and lipids…and you do have to look at the cardiovascular disease outcome [too]”.

According to GlobalData’s Pharma Intelligence Center, there are 35 Phase III candidates, 94 Phase II candidates, and 111 Phase I candidates for obesity globally. As for CVD, there are 96 Phase III candidates, 201 Phase II candidates, and 206 Phase I candidates worldwide.