TIRZEPATIDE reduces the risk of cardiovascular death or worsening heart failure in patients with obesity-related HFpEF equally across levels of obesity, but those with higher BMI experience greater benefits in physical capacity and weight loss, according to new findings from the SUMMIT trial.
The secondary analysis of the phase 3 SUMMIT trial included 731 adults with heart failure with preserved ejection fraction (HFpEF) and BMI ≥30 kg/m², randomised to receive tirzepatide or placebo. Researchers examined whether baseline obesity severity – assessed by BMI and waist-height ratio (WHR) – influenced tirzepatide’s effects on the risk of cardiovascular death or worsening heart failure, and on secondary outcomes such as the Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CSS), six-minute walk distance (6MWD), C-reactive protein (CRP), and body weight at 52 weeks. Time-to-event endpoints were analysed with Cox regression, and continuous outcomes with mixed-effects models.
Patients with higher BMI were generally younger, more likely to be women, and presented greater heart failure severity and systemic inflammation than those with lower BMI. High WHR was linked to poorer exercise capacity and renal function. The benefit of tirzepatide in reducing the risk of cardiovascular death or worsening heart failure was observed irrespective of baseline BMI or WHR tertile. However, greater gains in 6MWD (estimated treatment difference [ETD]: 9.9 m to 37.5 m; P = 0.025), weight loss (ETD: −10.7% to −14.4%; P = 0.006), and systolic blood pressure (ETD: −1.00 to −6.62 mm Hg; P = 0.035) arose among those with higher BMI. Greater weight and waist circumference reduction were associated with further improvements in exercise capacity and quality of life.
These findings suggest tirzepatide should be considered irrespective of obesity severity in patients with HFpEF, while clinicians may observe especially robust improvements in physical function and weight loss among those with higher BMI. Ongoing research will help establish whether tailoring therapy by obesity distribution provides additional clinical value.
Reference
Borlaug BA et al. SUMMIT Trial Study Group. Impact of body mass index, central adiposity, and weight loss on the benefits of tirzepatide in HFpEF: the SUMMIT trial. Journal of the American College of Cardiology. 2025;86(4):242-55.
