Lauren Terp, PharmD, Park Nicollet Health Services
Background
Obesity is a well-recognized and modifiable risk factor for heart failure (HF), contributing to both preserved (HFpEF) and reduced ejection fraction (HFrEF), and worsening outcomes in established disease. In June 2025, the American College of Cardiology (ACC) released a Scientific Statement on obesity management in adults with HF, with emphasis on stage 2 HFpEF. Nearly 42% of U.S. adults meet body mass index (BMI) criteria for obesity. Shared genetic, environmental, psychological, and nutritional factors underlie the strong overlap between obesity and HF. Epidemiologic data show that each 4 kg/m2 increase in BMI raises the adjusted risk of HF by 1.2-fold, particularly in HFpEF. This overlap underscores the challenge of achieving effective weight loss while balancing the complex pathophysiology and individualized goals of HF care.
Pharmacologic Therapy Evidence
Recent clinical trial data have increased interest in the role of anti-obesity medications (AOMs) in HF. Glucagon-like peptide-1 (GLP-1) receptor agonists and dual glucose-dependent insulinotropic polypeptide (GIP)/GLP-1 receptor agonists have demonstrated substantial weight reduction in individuals with obesity, including those with cardiovascular disease.
- Semaglutide: The STEP-HFpEF trial enrolled 529 patients with obesity and HFpEF. At 52 weeks, semaglutide 2.4 mg weekly produced a –13.3% mean weight reduction versus –2.6% with placebo (difference –10.7%). The KCCQ Clinical Summary Score, a patient-reported outcome measure used to assess symptom frequency, burden, and physical limitations in individuals with heart failure. This metric improved by 16.6 points vs 8.7 points with placebo (difference +7.8 points; p<0.001). 6-minute walk distance increased by 21.5 m with semaglutide vs 1.2 m with placebo. NT-proBNP fell by –20% vs –5%, and HF hospitalizations/urgent visits were numerically lower (1 vs 12 events).
- Tirzepatide: The SUMMIT trial enrolled 731 patients with obesity and HFpEF. At 52 weeks, tirzepatide achieved a –13.9% mean weight reduction vs –2.2% with placebo (difference –11.7%). The KCCQ Clinical Summary Score improved by 19.5 vs 12.7 points (difference +6.8; p<0.001). 6-minute walk distance increased by 26.0 m vs 10.1 m. NT-proBNP decreased more substantially (–23.6% vs –5.8%). Importantly, tirzepatide showed a statistically significant 38% relative risk reduction in the composite of CV death or worsening HF events (driven mainly by fewer HF hospitalizations), marking the first pharmacotherapy trial in obesity-related HFpEF to demonstrate event-level benefit.
Other Anti-Obesity Medications (AOMs)
Earlier-generation agents (e.g., orlistat, phentermine/topiramate, naltrexone/bupropion) are briefly reviewed in the statement but are associated with more modest weight loss (5–10%), limited HF-specific evidence, and a less favorable safety profile in patients with advanced cardiovascular disease. As discussed in the ACC statement, their role in HF remains uncertain, and they are not emphasized as primary strategies in the statement.
Evidence Gaps
Despite encouraging results, key questions remain. It is unclear whether improvements in HF outcomes are driven primarily by weight loss or direct cardioprotective effects of GLP-1/GIP agonists. Evidence in HFrEF is limited, as these patients have been largely excluded from trials. Comparative effectiveness data between pharmacologic therapies and metabolic surgery are lacking, and the durability of benefits beyond two years remains uncertain. This uncertainty underscores the need for additional mechanistic research.
Discussion
The ACC statement reframes obesity as a modifiable driver of HF pathophysiology, rather than a secondary comorbidity. This shift opens the door to more proactive management strategies—particularly in HFpEF, where therapeutic options have historically been limited. The emergence of highly effective AOMs offers new possibilities, but equitable access to therapy is also a central theme. Cost, insurance requirements, and limited availability of support services can prevent patients—especially those most affected by HF—from receiving evidence-based obesity treatment. Addressing these barriers will require coordinated efforts across the care team. Pharmacists are well-positioned to navigate prior authorizations, connect patients with assistance programs, and provide counseling to optimize adherence and monitor for adverse effects.
Clinical Impact
For pharmacy and multidisciplinary teams, the statement’s recommendations translate into several practice priorities. Firstly, pharmacists can continue to advocate for providers to assess beyond BMI alone when evaluating obesity in patients with heart failure by incorporating waist circumference, glycemic control, and functional status into medication reviews and care plans. Second, evaluate whether the appropriate application of GLP-1 or GIP/GLP-1 receptor agonists for HFpEF patients with obesity, ensuring careful consideration of comorbidities. Finally, proactively address medication access barriers by streamlining prior authorization processes and offering patient education to support treatment success.
Published on November 17th, 2025.
References
- Kittleson MM, Benjamin E, Blumer V, et al. 2025 ACC Scientific Statement on the Management of Obesity in Adults With Heart Failure. J Am Coll Cardiol. 2025;85(2):e107-e128. doi:10.1016/j.jacc.2025.05.008
- Hales CM, Carroll MD, Fryar CD, Ogden CL. Prevalence of obesity among adults and youth: United States, 2017–2020. NCHS Data Brief. 2021;438:1-8.
- Jensen MD, Ryan DH, Apovian CM, et al. 2023 AHA/ACC/TOS Guideline for the Management of Overweight and Obesity in Adults. Circulation. 2023;147(7):e90-e109.
- Solomon SD, Vaduganathan M, Claggett BL, et al. Semaglutide in Patients with HFpEF. N Engl J Med. 2023;389(3):132-143.
- Packer M, Zile MR, Kramer CM, et al; SUMMIT Trial Study Group. Tirzepatide for heart failure with preserved ejection fraction and obesity. N Engl J Med. 2024;391(9):837-848. doi:10.1056/NEJMoa2410027.