January 16, 2026
3 min read
Key takeaways:
- BMI reduction below 25 kg/m2 with tirzepatide was linked to improved 10-year ASCVD risk.
- Lower BMI was also linked to improvements in blood pressure and lipids.
Individuals who achieved a BMI of less than 25 kg/m2 in the SURMOUNT trials of tirzepatide also experienced significant improvement in predicted 10-year atherosclerotic cardiovascular disease risk, researchers reported.
Participants who achieved a BMI of less than 25 kg/m2 were more likely to be assigned to tirzepatide (Zepbound, Eli Lilly) vs. placebo, to be women and to have lower baseline BMI compared with those who did not, according to the study.
A pooled analysis of three tirzepatide trials — SURMOUNT-1, SURMOUNT-3 and SURMOUNT-CN — evaluating the impact of achieving lower BMI on 10-year ASCVD risk and other cardiometabolic risk factors was published in eClinicalMedicine.
“To our knowledge, this is the first study to investigate the association between achieving BMI < 25 kg/m2 and long-term predicted ASCVD risk among individuals with obesity or overweight,” Lixin Guo, MD, PhD, of the department of endocrinology, Beijing Hospital, National Center of Gerontology and the Institute of Geriatric Medicine at the Chinese Academy of Medical Sciences in Beijing, and colleagues wrote. “This study found that participants who achieved BMI < 25 kg/m2 after 52 or 72 weeks of tirzepatide or placebo treatment had significantly greater reductions in 10-year predicted ASCVD risk compared with those who did not.”
The SURMOUNT trials
SURMOUNT-1, SURMOUNT-3 and SURMOUNT-CN were all phase 3, multicenter, randomized, double-blind, placebo-controlled trials. In SURMOUNT-1 and SURMOUNT-3, participants from multiple countries were randomly assigned to tirzepatide or placebo for 72 weeks. In SURMOUNT-CN, participants were assigned to tirzepatide or placebo for 52 weeks and were enrolled exclusively from China.
All SURMOUNT trials enrolled participants with overweight or obesity without diabetes.
As Healio previously reported, in SURMOUNT-1, almost all participants assigned to tirzepatide experienced 5% or more weight loss over 72 weeks vs. placebo, with at least 20% weight loss in more than half of participants receiving the highest dose. In SURMOUNT-3, participants assigned to tirzepatide for 72 weeks following a 12-week intensive lifestyle intervention achieved a mean weight loss of more than 24%.
The results of SURMOUNT-CN were published in JAMA in 2024. In that trial, the proportion of participants who achieved weight reductions of 5% or more was 87.7% among those assigned to tirzepatide 10 mg, 85.8% among those assigned to tirzepatide 15 mg and 29.3% of those assigned to placebo.
For the present analysis, researchers pooled data from the three SURMOUNT trials to evaluate the impact of achieving BMI of less than 25 kg/m2 on 10-year ASCVD risk as calculated by the American Heart Association/American College of Cardiology Pooled Cohort Equations.
Impact of lower BMI on ASCVD risk
Among the cohort of 2,691 participants (mean age, 45 years; 66% women), 18.4% achieved BMI of less than 25 kg/m2 at trial end.
Participants who achieved a BMI of less than 25 kg/m2 were more often assigned to tirzepatide (98.2% vs. 66.8%), more often women (79.6% vs. 63.4%) and with lower mean BMI at baseline compared with those whose BMI remained above 25 kg/m2 at trial end (32.3 kg/m2 vs. 38.2 kg/m2; P for all < .001).
After adjusting for baseline covariates, participants who achieved a BMI of less than 25 kg/m2 experienced greater reduction in 10-year ASCVD risk compared with those who did not (39.4% vs 10.6%; P < .001), according to the study.
The researchers also observed that participants who had baseline intermediate to high ASCVD risk and achieved a BMI of less than 25 kg/m2 experienced greater reduction in predicted 10-year ASCVD risk vs. those whose BMI remained above 25 kg/m2 (25.6% vs. 9%; P < .001).
“Weight reduction targets that are suitable for the long term are needed to optimize cardiovascular outcomes,” the researchers wrote. “Discussions reconsidering the percent weight reduction targets as well as more specific recommendations on the BMI target have been emerging.”
In other findings, participants who achieved a BMI of less than 25 kg/m2 in the SURMOUNT trials experienced greater improvements in BP and lipids vs. those who did not (P for all < .001).
“As more data with longer follow-ups become available, future studies are warranted to evaluate the association between BMI < 25 kg/m2 and observed incident ASCVD risk,” the researchers wrote. “Future clinical guidelines might consider evaluating benefits and risks of targeting BMI < 25 kg/m2 for individuals with obesity or overweight, particularly for those at a high risk of cardiovascular events.”
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