J Am Coll Cardiol

Tirzepatide delivers greater HFpEF benefits in patients with higher BMI

July 25, 2025

Tirzepatide demonstrates clinical benefit across the obesity spectrum in heart failure with preserved ejection fraction (HFpEF), with patients who have higher baseline BMI or achieve greater weight loss experiencing the most substantial gains in functional capacity and quality of life.

Study details. This secondary analysis of the SUMMIT trial (NCT04847557) examined the influence of BMI, waist circumference, and weight loss on the effects of tirzepatide in patients with obesity-related HFpEF. Patients with NYHA class II-IV HFpEF and BMI ≥30 kg/m² were randomized to tirzepatide (n=364) or placebo (n=367). Primary outcomes: time to cardiovascular death or worsening HF and change in Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CSS) at 52 weeks. Key secondary outcomes: changes in 6-minute walk distance (6MWD), C-reactive protein, and body weight at 52 weeks. Primary and secondary endpoints were analyzed based on obesity severity (BMI) and distribution (waist-height ratio [WHR]).

Results. Tirzepatide consistently reduced the risk of heart failure events across all BMI and WHR groups. However, patients with higher baseline BMI experienced more pronounced benefits. Improvements in 6MWD increased across BMI tertiles, with estimated treatment differences of +9.9 m, +26.3 m, and +37.5 m from lowest to highest tertile (all P=0.025). Similarly, body weight reductions were greater in those with higher BMI: –10.7%, –11.8%, and –14.4%, respectively (all P=0.006). Systolic BP also declined more in higher BMI groups. Among patients receiving tirzepatide, greater weight and waist circumference reductions were associated with larger improvements in 6MWD, KCCQ-CSS, CRP, and BP. Notably, individuals with elevated WHR but lower BMI had worse baseline functional status, higher NT-proBNP, and poorer renal function compared with those with higher BMI but lower WHR.

Source:

Borlaug BA, et al; SUMMIT Trial Study Group. (2025, July 29). J Am Coll Cardiol. Impact of Body Mass Index, Central Adiposity, and Weight Loss on the Benefits of Tirzepatide in HFpEF: The SUMMIT Trial. https://pubmed.ncbi.nlm.nih.gov/40701669/