Log in

Anti-obesity medications in the management of heart failure with preserved ejection fraction: available evidence and next STEPS

  • Mini Review
  • Published:
Heart Failure Reviews Aims and scope Submit manuscript

Abstract

Obesity is associated with an increased risk of incident heart failure with preserved ejection fraction (HFpEF) and, among patients with existing heart failure, is associated with worse quality of life, higher symptom burden, and more HF hospitalizations. Anti-obesity medication (AOM) semaglutide has been shown to be efficacious at both causing intentional weight loss and improving HF symptom burden, with some evidence to suggest that HF clinical events may also be reduced. Additional ongoing trials of AOM in patients with cardiovascular disease, including HFpEF, will further improve insight into the potential role of managing obesity to improve HF status among patients with HFpEF and obesity.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or Ebook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price includes VAT (France)

Instant access to the full article PDF.

Fig. 1

References

  1. Pandey A, LaMonte M, Klein L et al (2017) Relationship between physical activity, body mass index, and risk of heart failure. J Am Coll Cardiol 69:1129–1142

    Article  PubMed  PubMed Central  Google Scholar 

  2. Kenchaiah S, Evans JC, Levy D et al (2002) Obesity and the risk of heart failure. N Engl J Med 347:305–313

    Article  PubMed  Google Scholar 

  3. Borlaug BA, Jensen MD, Kitzman DW, Lam CSP, Obokata M, Rider OJ (2022) Obesity and heart failure with preserved ejection fraction: new insights and pathophysiological targets. Cardiovasc Res cvac120

  4. Obokata M, Reddy YNV, Pislaru SV, Melenovsky V, Borlaug BA (2017) Evidence supporting the existence of a distinct obese phenotype of heart failure with preserved ejection fraction. Circulation 136:6–19

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Adamson C, Kondo T, Jhund P et al (2022) Dapagliflozin for heart failure according to body mass index: the DELIVER trial. Eur Heart J 43:4406–4417

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Anker SD, Butler J, Filippatos G et al (2021) Empagliflozin in heart failure with a preserved ejection fraction. NEJM. 385:1451–1461

    Article  CAS  PubMed  Google Scholar 

  7. Sattar N, Butler J, Lee MM et al (2024) Body mass index and cardiorenal outcomes in the EMPEROR-Preserved trial: principal findings and meta-analysis with the DELIVER trial. Eur J Heart Fail. Published online 1 April 2024. https://doi.org/10.1002/ejhf.3221

  8. Joyce E, Lala A, Stevens SR et al (2016) Prevalence, profile, and prognosis of severe obesity in contemporary hospitalized heart failure trial populations. JACC Heart Fail 4:923–931

    Article  PubMed  PubMed Central  Google Scholar 

  9. The LOOK AHEAD Investigators (2013) Cardiovascular effects of intensive lifestyle intervention in type 2 diabetes. N Engl J Med 369:145–154

    Article  Google Scholar 

  10. El Hajj EC, El Hajj MC, Sykes B et al (2021) Pragmatic weight management program for patients with obesity and heart failure with preserved ejection fraction. J Am Heart Assoc 10:e022930

    Article  PubMed  PubMed Central  Google Scholar 

  11. Kolata G. How Fen-Phen (1997) A diet “miracle,” rose and fell. The New York Times.

  12. James WPT, Caterson ID, Coutinho W et al (2010) Effect of sibutramine on cardiovascular outcomes in overweight and obese subjects. N Engl J Med 363:905–917

    Article  CAS  PubMed  Google Scholar 

  13. Colman E, Golden J, Roberts M, Egan A, Weaver J, Rosebraugh C (2012) The FDA’s assessment of two drugs for chronic weight management. N Engl J Med 367:1577–1579

    Article  CAS  PubMed  Google Scholar 

  14. Blüher M, Aras M, Aronne LJ et al (2023) New insights into the treatment of obesity. Diabetes Obes Metab 25:2058–2072

    Article  PubMed  Google Scholar 

  15. Harrington J, Felker GM, Lingvay I, Pagidipati NJ, Pandey A, McGuire DK (2024) Managing obesity in heart failure: a chance to tip the scales? JACC Heart Fail 12:28–34

    Article  PubMed  Google Scholar 

  16. Wilding JPH, Batterham RL, Calanna S et al (2021) Once-weekly semaglutide in adults with overweight or obesity. N Engl J Med 384:989–1002

    Article  CAS  PubMed  Google Scholar 

  17. Kosiborod MN, Abildstrøm SZ, Borlaug BA et al (2023) Semaglutide in patients with heart failure with preserved ejection fraction and obesity. N Engl J Med 389:1069–1084

    Article  CAS  PubMed  Google Scholar 

  18. Kosiborod MN, Petrie MC, Borlaug BA et al (2024) Semaglutide in patients with obesity-related heart failure and type 2 diabetes. N Engl J Med 390:1394–1407

    Article  CAS  PubMed  Google Scholar 

  19. Deanfield JE (2024) Semaglutide and cardiovascular outcomes in patients with overweight or obesity and heart failure: a pre-specified analysis from the select tria.l Euro Soc Cardiol Heart Fail Congress

  20. Spertus JA, Jones PG, Sandhu AT, Arnold SV (2020) Interpreting the Kansas City Cardiomyopathy Questionnaire in clinical trials and clinical care: JACC state-of-the-art review. J Am Coll Cardiol 76:2379–2390

    Article  PubMed  Google Scholar 

  21. Madamanchi C, Alhosaini H, Sumida A, Runge MS (2014) Obesity and natriuretic peptides, BNP and NT-proBNP: mechanisms and diagnostic implications for heart failure. Int J Cardiol 176:611–617

    Article  PubMed  PubMed Central  Google Scholar 

  22. Hollstein T, Schlicht K, Krause L et al (2021) Effect of various weight loss interventions on serum NT-proBNP concentration in severe obese subjects without clinical manifest heart failure. Sci Rep 11:10096

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Shah SJ, Sharma K, Borlaug BA et al (2024) Semaglutide and diuretic use in obesity-related heart failure with preserved ejection fraction: a pooled analysis of the STEP-HFpEF and STEP-HFpEF-DM trials. Eur Heart J ehae322

  24. Davies M, Færch L, Jeppesen OK et al (2021) Semaglutide 2·4 mg once a week in adults with overweight or obesity, and type 2 diabetes (STEP 2): a randomised, double-blind, double-dummy, placebo-controlled, phase 3 trial. The Lancet 397:971–984

    Article  CAS  Google Scholar 

  25. Lincoff AM, Brown-Frandsen K, Colhoun HM et al (2023) Semaglutide and cardiovascular outcomes in obesity without diabetes. N Engl J Med 389:2221–2232

    Article  CAS  PubMed  Google Scholar 

  26. Lingvay I, Brown-Frandsen K, Colhoun HM et al (2023) Semaglutide for cardiovascular event reduction in people with overweight or obesity: SELECT study baseline characteristics. Obesity (Silver Spring) 31:111–122

    Article  CAS  PubMed  Google Scholar 

  27. Jastreboff AM, Aronne LJ, Ahmad NN et al (2022) Tirzepatide once weekly for the treatment of obesity. N Engl J Med 387:205–216

    Article  CAS  PubMed  Google Scholar 

  28. Eli Lilly and Company. A study of tirzepatide (LY3298176) in participants with heart failure with preserved ejection fraction and obesity. ClinicalTrials.gov.  Accessed 22 July 2023. https://clinicaltrials.gov/ct2/show/NCT04847557

  29. Eli Lilly and Company. A study of tirzepatide (LY3298176) on the reduction on morbidity and mortality in adults with obesity (SURMOUNT-MMO) Accessed 8 July 2023. https://clinicaltrials.gov/study/NCT05556512

  30. Novo Nordisk A/S (2023) The cardiovascular safety of cagrilintide 2.4 mg s.c. in combination with semaglutide 2.4 mg s.c. (CagriSema 2.4 mg/2.4 mg s.c.) once-weekly in participants with obesity and established cardiovascular disease. clinicaltrials.gov

  31. Frias JP, Deenadayalan S, Erichsen L et al (2023) Efficacy and safety of co-administered once-weekly cagrilintide 2·4 mg with once-weekly semaglutide 2·4 mg in type 2 diabetes: a multicentre, randomised, double-blind, active-controlled, phase 2 trial. Lancet 402:720–730

    Article  CAS  PubMed  Google Scholar 

  32. Eli Lilly and Company (2023) A phase 3, randomized, double-blind study to investigate the efficacy and safety of once-daily oral LY3502970 compared with placebo in adult participants with obesity or overweight with weight-related comorbidities (ATTAIN-1). clinicaltrials.gov.

  33. Eli Lilly and Company (2023) A phase 3, open-label study of once daily LY3502970 compared with insulin glargine in adult participants with type 2 diabetes and obesity or overweight at increased cardiovascular risk. clinicaltrials.gov.

  34. Anon. Altimmune obesity drug well-positioned despite safety data. BioSpace Accessed 3 Sept 2023. https://www.biospace.com/article/altimmune-shares-plunge-on-obesity-data-over-safety-concerns-/

  35. Boehringer Ingelheim (2024) A phase 3, randomised, double-blind, parallel-group, event-driven, cardiovascular safety study with BI 456906 administered subcutaneously compared with placebo in participants with overweight or obesity with established cardiovascular disease (CVD) or chronic kidney disease, and/or at least two weight-related complications or risk factors for CVD. clinicaltrials.gov.

  36. Jastreboff AM, Kaplan LM, Frías JP et al (2023) Triple–hormone-receptor agonist retatrutide for obesity — a phase 2 trial. N Engl J Med 389:514–526

    Article  CAS  PubMed  Google Scholar 

  37. Eli Lilly and Company (2023) A randomized, double-blind, phase 3 study to investigate the efficacy and safety of LY3437943 once weekly compared to placebo in participants with severe obesity and established cardiovascular disease. clinicaltrials.gov.

  38. Noureddin M, Khan S, Portell F et al (2023) Safety and efficacy of once-daily HU6 versus placebo in people with non-alcoholic fatty liver disease and high BMI: a randomised, double-blind, placebo-controlled, phase 2a trial. Lancet Gastroenterol Hepatol 8:1094–1105

    Article  PubMed  Google Scholar 

  39. Horwich TB, Fonarow GC, Clark AL (2018) Obesity and the obesity paradox in heart failure. Prog Cardiovasc Dis 61:151–156

    Article  PubMed  Google Scholar 

  40. Bikou A, Dermiki-Gkana F, Penteris M, Constantinides TK, Kontogiorgis C (2024) A systematic review of the effect of semaglutide on lean mass: insights from clinical trials. Expert Opin Pharmacother 25:611–619

    Article  CAS  PubMed  Google Scholar 

  41. Rivus Pharmaceuticals, Inc. (2023) Exploratory phase 2a, double-blind, placebo-controlled, dose escalation study to determine the safety, tolerability, PD, and PK of HU6 for the treatment of subjects with obese Heart Failure with Preserved Ejection Fraction (HFpEF). clinicaltrials.gov

  42. Rubino D, Abrahamsson N, Davies M et al (2021) Effect of continued weekly subcutaneous semaglutide vs placebo on weight loss maintenance in adults with overweight or obesity: the STEP 4 randomized clinical trial. JAMA 325:1414–1425

    Article  CAS  PubMed  Google Scholar 

  43. Wilding JPH, Batterham RL, Davies M et al (2022) Weight regain and cardiometabolic effects after withdrawal of semaglutide: the STEP 1 trial extension. Diabetes Obes Metab 24:1553–1564

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Bozkurt B, Aguilar D, Deswal A et al (2016) Contributory risk and management of comorbidities of hypertension, obesity, diabetes mellitus, hyperlipidemia, and metabolic syndrome in chronic heart failure: a scientific statement from the American Heart Association. Circulation 134:e535–e578

    Article  PubMed  Google Scholar 

  45. Vest AR, Chan M, Deswal A et al (2019) Nutrition, obesity, and cachexia in patients with heart failure: a consensus statement from the Heart Failure Society of America Scientific Statements Committee. J Card Fail 25:380–400

    Article  PubMed  Google Scholar 

  46. Ponikowski P, Voors AA, Anker SD et al (2016) ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure The Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC)Developed with the special contribution of the Heart Failure Association (HFA) of the ESC. Eur Heart J 37:2129–2200

    Article  PubMed  Google Scholar 

  47. Borlaug BA, Kitzman DW, Davies MJ et al (2023) Semaglutide in HFpEF across obesity class and by body weight reduction: a prespecified analysis of the STEP-HFpEF trial. Nat Med 29:2358–2365

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Contributions

Manuscript drafted, written, and revised by JH.

Corresponding author

Correspondence to Josephine Harrington.

Ethics declarations

Conflict of interest

JH is an Associate Editor of the journal; she reports no other disclosures.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Harrington, J. Anti-obesity medications in the management of heart failure with preserved ejection fraction: available evidence and next STEPS. Heart Fail Rev (2024). https://doi.org/10.1007/s10741-024-10410-0

Download citation

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s10741-024-10410-0

Keywords

Navigation