# Achieving BMI <25 kg/m2 was associated with reduced predicted risk of atherosclerotic cardiovascular disease in people with obesity or overweight on tirzepatide or placebo: a post hoc analysis of SURMOUNT-1, -3, and -CN

## TL;DR

Losing enough weight to achieve a BMI under 25 significantly reduces cardiovascular disease risk in overweight or obese individuals, especially when using tirzepatide.

## Contribution

This study shows that achieving a BMI <25 with tirzepatide leads to greater cardiovascular risk reduction than maintaining a higher BMI.

## Key findings

- Participants achieving BMI <25 had a 39.4% reduction in predicted ASCVD risk compared to 10.6% in the BMI ≥25 group.
- Those with intermediate-to-high baseline ASCVD risk saw a 25.6% reduction in the BMI <25 group versus 9.0% in the BMI ≥25 group.
- BMI <25 was associated with greater improvements in blood pressure and lipids compared to the BMI ≥25 group.

## Abstract

Effective weight reduction interventions may significantly reduce obesity-related atherosclerotic cardiovascular disease (ASCVD) risk. However, evidence on the association between optimal body mass index (BMI) target and long-term ASCVD risk was limited.

Pooled individual-level data from participants with obesity/overweight randomized to tirzepatide or placebo in SURMOUNT-1 (December 2019–April 2022; NCT04184622), -3 (March 2021–April 2023; NCT04657016), and -CN trials (September 2021–December 2022; NCT05024032) were analyzed. Ten-year ASCVD risk was calculated using the American College of Cardiology/American Heart Association Pooled Cohort Equations. A mixed model for repeated measures analysis was used to compare percent change in ASCVD risk from baseline by achieved BMI group (<25 kg/m2, ≥25 kg/m2) at trial end, with terms including achieved BMI group, time point, achieved-BMI-group-by-time-point interaction, and baseline covariates.

Among 2691 participants included, 495 (18.4%) achieved BMI <25 kg/m2 at trial end. In addition to a significantly higher proportion being treated with tirzepatide (98.2% vs 66.8%), the BMI <25 kg/m2 group also had a higher proportion of females and lower mean BMI at baseline compared with the BMI ≥25 kg/m2 group (P < 0.001 for all). After adjusting for baseline covariates, relative to baseline, participants achieving BMI <25 kg/m2 had a significantly greater percent reduction in predicted ASCVD risk (39.4% vs 10.6%, P < 0.001) compared to the BMI ≥25 kg/m2 group. Among those with baseline intermediate-to-high ASCVD risk, reduction remained greater in the BMI <25 kg/m2 group (25.6%) than the BMI ≥25 kg/m2 group (9.0%; P < 0.001). Significantly greater improvements were also observed in blood pressure and lipids for the BMI <25 kg/m2 group (P < 0.001).

Achieving BMI <25 kg/m2, primarily with tirzepatide, was associated with a significantly greater 10-year ASCVD risk reduction compared with those whose BMI remained at 25 kg/m2 or greater. These findings suggest potential cardiovascular benefits associated with targeting BMI <25 kg/m2 in the long-term weight management.

This study was funded by 10.13039/100004312Eli Lilly and Company.