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Worth Their Weight? An Update on New and Emerging Pharmacologic Agents for Obesity and Their Potential Role for Persons with Cardiac Conditions

  • Cardiometabolic Disease (DM and CV) (CJ Lavie, Section Editor)
  • Published:
Current Cardiology Reports Aims and scope Submit manuscript

Abstract

Purpose of Review

Obesity is associated with cardiovascular (CV) conditions, including but not limited to atherosclerotic disease, heart failure, and atrial fibrillation. Despite this, the impact of intentional weight loss on CV outcomes for persons with obesity and established CV conditions remains poorly studied. New and emerging pharmacologic therapies for weight loss primarily targeting the incretin/nutrient sensing axes induce substantial and sustained weight loss. The glucagon-like-peptide 1 receptor agonists (GLP-1 RA) liraglutide and semaglutide have US FDA approval for the treatment of obesity, and the application for an obesity indication for the dual GLP-1/glucose-dependent insulinotropic polypeptide (GIP) receptor agonist tirzepatide is presently under FDA review. Extensive phase II and IIIa randomized controlled trials are underway evaluating permutations of combined GLP-1 RA, GIP receptor agonist, GIP receptor antagonist, and glucagon receptor agonists. Clinical outcome trials of these therapies in persons with obesity at high risk of established CV conditions should make it possible to estimate the role of intentional weight loss in managing CV risk via these medications.

Recent Findings

High-dose once weekly injectable semaglutide (2.4 mg/week) use among persons with obesity and heart failure with preserved ejection fraction was effective at both reducing weight and improving health status; exercise capacity was also improved. Ongoing CV outcome trials of oral semaglutide and once weekly injectable tirzepatide will help to establish the role of these therapies among persons with other CV conditions. In addition to these two therapies targeting a CV claim or indication, many other new therapeutics for weight loss, as reviewed, are currently in development.

Summary

The impact of pharmacologic-induced weight loss on CV conditions for persons with obesity and established CV conditions is currently under investigation for multiple agents. These therapies may offer new avenues to manage CV risk in persons with obesity and with established or at high risk for CV disease.

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Data Availability

No datasets were generated or analysed during the current study.

References

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Authors and Affiliations

  1. Division of Cardiology, Department of Internal Medicine, Duke University Medical Center, Durham North Carolina, Durham, USA

    Josephine Harrington, G. Michael Felker & Neha J. Pagidipati

  2. Duke Clinical Research Institute, Durham, NC, USA

    Josephine Harrington, G. Michael Felker & Neha J. Pagidipati

  3. Cardiology Division, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA

    James L. Januzzi

  4. Baim Institute for Clinical Research, Boston, MA, USA

    James L. Januzzi, Carolyn S. P. Lam & Harriette G. C. Van Spall

  5. National Heart Centre Singapore and Duke-National University of Singapore, Singapore, Singapore

    Carolyn S. P. Lam

  6. Division of Endocrinology, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, USA

    Ildiko Lingvay

  7. Peter O’Donnell Jr School of Public Health, University of Texas Southwestern Medical Center, Dallas, TX, USA

    Ildiko Lingvay

  8. School of Cardiovascular and Metabolic Health, University of Glasgow, Glasgow, UK

    Naveed Sattar

  9. Research Institute of St. Joseph’s, Hamilton, Canada

    Harriette G. C. Van Spall

  10. McMaster University Faculty of Health Sciences, Hamilton, Canada

    Harriette G. C. Van Spall

  11. Division of Cardiac Surgery, St Michael’s Hospital of Unity Health Toronto, Toronto, ON, Canada

    Subodh Verma

  12. Department of Surgery, and Pharmacology and Toxicology, University of Toronto, Toronto, ON, Canada

    Subodh Verma

  13. Division of Cardiology, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, USA

    Darren K. McGuire

  14. Parkland Health, Dallas, TX, USA

    Darren K. McGuire

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JH and DM wrote the main manuscript text and JH prepared the table. All authors reviewed the manuscript.

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Correspondence to Josephine Harrington.

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Conflict of Interest

JH has no disclosures. GMF has received research grants from NHLBI, American Heart Association, Amgen, Bayer, BMS, Novartis, Daxor, Merck, Cytokinetics, and CSL-Behring; he has acted as a consultant to Novartis, Amgen, BMS, Cytokinetics, Innolife, Medtronic, Cardionomic, Boehringer Ingelheim, American Regent, Abbott, Astra-Zeneca, Regeneron, Reprieve, Myovant, Sequana, Windtree Therapeutics, Rocket Pharma, and Whiteswell; and has served on clinical endpoint committees/data safety monitoring boards for Amgen, Merck, Medtronic, EBR Systems, V-Wave, and LivaNova. JLJ is a Trustee of the American College of Cardiology; is a board member of Imbria Pharmaceuticals; reports has received research support for Clinical Trials Leadership from Abbott Diagnostics, Applied Therapeutics, HeartFlow, Innolife, and Novartis; has received consulting income from Abbott Diagnostics, AstraZeneca, Beckman Coulter, Jana Care, Janssen, Novartis, Prevencio, Quidel, and Roche Diagnostics; and participates in clinical endpoint committees/data safety monitoring boards for AbbVie, Abbott, Bayer, Intercept, Siemens, Pfizer, and Takeda. IL received research funding (paid to institution) from Novo Nordisk, Sanofi, Merck, Pfizer, Mylan, and Boehringer-Ingelheim. IL received advisory/consulting fees and/or other support from Novo Nordisk, Eli Lilly, Sanofi, Astra Zeneca, Boehringer-Ingelheim, Johnson and Johnson, Intercept, TARGETPharma, Merck, Pfizer, Valeritas, Zealand Pharma, Shionogi, Carmot Therapeutics, Structure Therapeutics, Bayer, Translational Medical Academy, Mediflix, Biomea, The Comm Group, and WebMD and serves on the Data Safety Monitoring Board for JAEB. SV holds a Tier 1 Canada Research Chair in Cardiovascular Surgery; and reports receiving research grants and/or speaking honoraria from Amarin, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Canadian Medical and Surgical Knowledge Translation Research Group, Eli Lilly, HLS Therapeutics, Janssen, Novartis, Novo Nordisk, Pfizer, PhaseBio, S & L Solutions Event Management Inc., and Sanofi. He is the President of the Canadian Medical and Surgical Knowledge Translation Research Group, a federally incorporated not-for-profit physician organization. CSPL is supported by a Clinician Scientist Award from the National Medical Research Council of Singapore; has Received research support from Novo Nordisk and Roche Diagnostics; has served as consultant or on the Advisory Board/Steering Committee/Executive Committee for Alleviant Medical, Allysta Pharma, AnaCardio AB, Applied Therapeutics, AstraZeneca, Bayer, Biopeutics, Boehringer Ingelheim, Boston Scientific, Bristol Myers Squibb, CardioRenal, Cytokinetics, Darma Inc., EchoNous Inc., Eli Lilly, Impulse Dynamics, Intellia Therapeutics, Ionis Pharmaceutical, Janssen Research & Development LLC, Medscape/WebMD Global LLC, Merck, Novartis, Novo Nordisk, Prosciento Inc., Quidel Corporation, Radcliffe Group Ltd., Recardio Inc., ReCor Medical, Roche Diagnostics, Sanofi, Siemens Healthcare Diagnostics and Us2.ai; and serves as co-founder and non-executive director of Us2.ai. NJP reports research support from Amgen, Boehringer Ingelheim, Eggland’s Best, Eli Lilly, Novartis, Novo Nordisk, and Verily Life Sciences; has served as a consultant or on an advisory panel for Bayer, Boehringer Ingelheim, CRISPR Therapeutics, Eli Lilly, Esperion, AstraZeneca, Merck, Novartis, and Novo Nordisk; and is an Executive Committee member for trials sponsored by Novo Nordisk and Amgen on DSMBs for trials sponsored by Janssen and Novartis. HVS is funded by the Canadian Institutes of Health Research. NS has consulted for and/or received speaker honoraria from Abbott Laboratories, Amgen, AstraZeneca, Boehringer Ingelheim, Eli Lilly, Hanmi Pharmaceuticals, Janssen, Merck Sharp & Dohme, Novartis, Novo Nordisk, Pfizer, Roche Diagnostics, and Sanofi and received grant support paid to his University from AstraZeneca, Boehringer Ingelheim, Novartis, and Roche Diagnostics outside the submitted work. DKM reports research support for Clinical Trials Leadership from Boehringer Ingelheim, Pfizer, AstraZeneca, Novo Nordisk, Esperion, Lilly USA, and CSL Behring and honoraria for consultancy from Lilly USA, Pfizer, Boehringer Ingelheim, Lexicon, Novo Nordisk, Applied Therapeutics, Altimmune, CSL Behring, Bayer, Intercept, and New Amsterdam.

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Harrington, J., Felker, G.M., Januzzi, J.L. et al. Worth Their Weight? An Update on New and Emerging Pharmacologic Agents for Obesity and Their Potential Role for Persons with Cardiac Conditions. Curr Cardiol Rep 26, 61–71 (2024). https://doi.org/10.1007/s11886-023-02016-z

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