Pharmacotherapy for obesity: recent evolution and implications for cardiovascular risk reduction

ABSTRACT

Introduction

Obesity is highly prevalent in the U.S. and is associated with an increased risk of major adverse cardiovascular events (MACE). Modalities for the management of obesity include lifestyle intervention, pharmacotherapy, and bariatric surgery.

Areas covered

This review describes the evidence on the effects of weight loss therapies on MACE risk. Lifestyle interventions and older antiobesity pharmacotherapies have been associated with <12% body weight reduction and no clear benefit to reduce MACE risk. Bariatric surgery is associated with substantial weight reduction (20–30%) and markedly lower subsequent risk for MACE. Newer antiobesity pharmacotherapies, particularly semaglutide and tirzepatide, have shown greater efficacy for weight reduction compared with older medications and are being evaluated in cardiovascular outcomes trials.

Expert opinion

Current practice for cardiovascular risk reduction in patients with obesity is lifestyle intervention for weight loss, combined with the treatment of obesity-related cardiometabolic risk factors individually. The use of medications to treat obesity is relatively rare. In part, this reflects concerns about long-term safety and weight loss effectiveness, possible provider bias, as well as lack of clear evidence of MACE risk reduction. If ongoing outcomes trials demonstrate the efficacy of newer agents in reducing MACE risk, this will likely lead to expanded use in obesity management.

KEYWORDS:

• Antiobesity pharmacotherapy
• bariatric surgery
• cardiometabolic risk
• cardiovascular disease
• lifestyle intervention
• obesity
• weight loss

Article highlights

• Obesity is highly prevalent in the U.S. and is associated with an increased risk of major adverse cardiovascular events (MACE).

• Modalities for the management of patients with obesity include lifestyle intervention, pharmacotherapy, and bariatric surgery.

• Lifestyle interventions and older antiobesity pharmacotherapies have been associated with body weight reductions of <12% and no clear benefit to reduce MACE risk.

• Some older antiobesity pharmacotherapies had safety issues and are no longer available in the U.S. (fenfluramine, lorcaserin, sibutramine), which has contributed to hesitancy to prescribe available antiobesity pharmacotherapies.

• Bariatric surgery has been associated with significant weight reduction (20-30%), improvements in cardiometabolic risk factors, and a markedly reduced risk of MACE.

• Newer antiobesity pharmacotherapies that are available or in development (semaglutide, tirzepatide) have been associated with greater weight loss efficacy than older agents.

• Trials are underway to assess the effects of semaglutide and tirzepatide on MACE risk in patients with overweight or obesity plus comorbidities.

• If trials with these newer agents demonstrate reduced MACE risk, this may usher in a new era for management of cardiovascular disease risk in patients with obesity.

Declaration of interest

During the last 24 months, KCM has received research funding and/or consulting fees from Eli Lilly and Co.; Novo Nordisk; 89Bio; New Amsterdam Pharmaceuticals; Acasti Pharmaceuticals; Beren Therapeutics; Matinas Biopharma; North Sea Therapeutics; General Mills; National Dairy Council; Hass Avocado Board; Pharmavite; Campbell’s; National Cattleman’s Beef Association/Beef Checkoff; Greenyn Biotechnology; Naturmega; Indiana University Foundation; Bragg Live Products; Cargill; Medifast; NeuroEnergy Ventures; Pepsico; Seed.

CFK is an employee of Midwest Biomedical Research and has no additional conflicts of interest to report beyond those disclosed for KCM.

During the last 24 months, DBA has received personal payments or promises for the same from Alkermes, Inc.; Amin Talati Wasserman of KSF Acquisition Corp. (Glanbia); Big Sky Health, Inc.; Clark Hill, PLC; Kaleido Biosciences; Law Offices of Ronald Marron; Medpace/Gelesis; Novo Nordisk Fonden; Sports Research Corp; and Tomasik, Kostin, and Kasserman.

DBA’s institution, Indiana University, and the Indiana University Foundation have received funds or donations to support his research or educational activities from: Alliance for Potato Research and Education; American Egg Board; Arnold Ventures; Eli Lilly and Company; Mars, Inc.; National Cattlemen’s Beef Association; Pfizer, Inc; Soleno Therapeutics; USDA; WW (formerly Weight Watchers); and numerous other for-profit and nonprofit organizations to support the work of the School of Public Health and the university more broadly.

During the last 24 months, KMG has received grant support from BioKier, Indiana University Foundation, and the National Institutes of Health.

The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.