Anti-obesity medications were associated with improvements in symptoms and functional capacity in patients with heart failure with preserved ejection fraction and obesity, according to a 2025 scientific statement from the American College of Cardiology (ACC).
The 2025 ACC Scientific Statement on the Management of Obesity in Adults With Heart Failure is the first major clinical guidance to address the intersection of obesity treatment and heart failure (HF), reflecting emerging data from randomized clinical trials of semaglutide and tirzepatide in this population.
Clinical Trial Findings
The STEP-HFpEF program, which enrolled 1,145 participants with HF with preserved ejection fraction (HFpEF) (left ventricular ejection fraction [LVEF] of 45% or greater) and body mass index (BMI) of 30 or greater, evaluated once-weekly semaglutide 2.4 mg. The semaglutide group demonstrated a placebo-corrected weight reduction of 8.4% (95% CI, –9.2% to –7.5%) and improvements in their Kansas City Cardiomyopathy Questionnaire–Clinical Summary Scores (KCCQ-CSS) by 7.5 points and 6-minute walk distance (6MWD) by 17.1 meters at 52 weeks.
The SUMMIT trial included 731 participants with HFpEF (LVEF of 50% or greater) and BMI of 30 or greater who were treated with once-weekly tirzepatide. Participants receiving tirzepatide achieved a placebo-corrected weight reduction of 11.6% (95% CI, –13.5% to –9.7%) and a 6.9-point improvement in KCCQ-CSS. The trial also included a co-primary endpoint of time to first HF event or cardiovascular death. Tirzepatide was associated with a hazard ratio of 0.62 (95% CI, 0.41–0.95) for this composite outcome, though further studies are needed to confirm effects on hard endpoints.
The statement notes that participants in these trials tended to be younger and have lower N-terminal pro–B-type natriuretic peptide (NT-proBNP) concentrations, higher LVEF, and higher BMIs than patients typically encountered in clinical practice, which may limit generalizability of findings.
Diagnostic Challenges and Considerations
The writing committee highlighted limitations in the use of BMI as a diagnostic tool in this population. “Although BMI is an inexpensive, easily acquired, and readily reproducible metric that is strongly embedded in research and clinical practice, significant limitations exist in the detection of excess adiposity, the location of adiposity, and applicability to diverse populations,” the statement notes.
For patients with a BMI less than 35, direct assessment of adiposity using anthropometric measures (waist circumference, waist-to-hip ratio, or waist-to-height ratio) or body composition analysis via dual-energy X-ray absorptiometry is recommended when feasible.
The statement proposes a diagnostic framework distinguishing “preclinical obesity” from “clinical obesity” based on the Lancet Diabetes and Endocrinology Commission. Individuals with HFpEF and obesity are classified as having clinical obesity, as excess adiposity contributes directly to cardiac dysfunction.
Natriuretic Peptide Interpretation
Natriuretic peptide concentrations are often lower in individuals with obesity, increasing the risk of underdiagnosis of HF. The statement reports that, in patients with a BMI greater than 35, a rule-out NT-proBNP threshold of more than 50 ng/L had 93% to 98% sensitivity, while a rule-in threshold of more than 220 ng/mL achieved 82% to 89% specificity. These are more accurate than standard thresholds, which demonstrated only 67% sensitivity in this population.
Medication Monitoring and Safety
Structured monitoring is advised during the initiation of anti-obesity medications. “During early-phase gradual dose escalation of semaglutide or tirzepatide, which occurs every 4 weeks, monitor kidney function and electrolytes with adjustment of diuretics, antihypertensive agents, and antihyperglycemic agents as indicated, particularly if gastrointestinal adverse effects are prominent,” the committee advises.
Metabolic and Bariatric Surgery
The statement discusses the role of metabolic and bariatric surgery (MBS) as a treatment option for select individuals with HF and obesity. “Metabolic and bariatric surgery appears effective for intentional weight loss and potentially to reduce risk of HF events, including hospitalization for HF and death, although these possibilities are based only on data from observational studies,” the statement explains.
However, individuals with HF undergoing MBS may face increased risk of postoperative cardiovascular morbidity and mortality. The committee recommends preoperative optimization and perioperative management by clinicians experienced in HF care.
Implementation and Evidence Gaps
Key knowledge gaps remain, including whether the observed benefits of GLP-1 receptor agonists are due primarily to weight loss or other mechanisms. The statement also notes that data are lacking for individuals with heart failure with reduced ejection fraction , in whom concerns about safety have been raised based on small studies of liraglutide.
The committee provides evidence-based selection criteria for FDA-approved anti-obesity therapies. Semaglutide is recommended for adults with HFpEF (LVEF of 45% or greater) and New York Heart Association (NYHA) functional class II through IV symptoms; tirzepatide is recommended for those with LVEF of 50% or greater. Both therapies require additional criteria, such as elevated left ventricular filling pressures or elevated NT-proBNP.
The statement concludes: “With accurate evaluation of obesity as well as administration and monitoring of safe and effective interventions, clinicians may improve quality of life and functional capacity and potentially reduce HF events in individuals living with HF and obesity.”