First study with positive cardiovascular outcome in obesity: Reflections on SELECT

Abstract

At present, medications of the GLP-1RA class, such as liraglutide 3.0 mg,²⁷ semaglutide 2.4 mg,²⁸ and tirzepatide (GLP-1/GIP [glucose-dependent insulinotropic polypeptide] agonist)²⁹ have been approved for weight management for adult patients with obesity or overweight with obesity-related complications. The previous study of semaglutide 2.4 mg in obese patients with heart failure, the STEP-HFpEF study,²² confirmed its significant improvement in clinical functional endpoints such as KCCQ-CSS score (Kansas City Cardiomyopathy Questionnaire clinical summary score) and 6MWD (6-Minute Walk Distance) for patients with heart failure and preserved/mildly reduced ejection fraction (HFpEF/HFmrEF), demonstrating the cardiovascular benefit of semaglutide 2.4 mg in patients with obesity. SELECT further confirmed that semaglutide 2.4 mg significantly reduced the risk of major cardiovascular events. As the first weight management drug with cardiovascular benefit confirmed by rigorous RCT globally, semaglutide 2.4 mg is of landmark significance and provides strong clinical evidence for the treatment of patients with CVD and overweight or obesity.

GLP-1RAs with proven cardiovascular benefits have been recommended by the guidelines as a first-line treatment for cardiovascular risk reduction in patients with T2DM and CVD or at high cardiovascular risk.³⁰ The SELECT further provided evidence for the use of high-dose GLP-1RA in a broader population of patients with overweight or obesity and CVD without T2DM.

CVD remains the principal cause of mortality both in China and globally. Overweight and obesity are not only significant risk factors for CVD but also as an independent chronic disease. With societal economic progress and lifestyle alterations, overweight and obesity have increasingly emerged as major societal concerns. Effective weight management necessitates a multidisciplinary, multilevel, and long-term comprehensive strategy that incorporates political, economic, environmental, social, and personal factors. Presently, the availability of new management options for obesity and CVD is expanding, and it is expected that these evidence-based treatments will overcome current clinical challenges, thereby better fulfilling the demands of clinical care.

QP made substantial contributions to the design of the study and drafted the manuscript. SF and TX calibrated the format and language of the article, while LG critically reviewed the manuscript. All authors have read and approved the final version to be published.

The study was supported by National High Level Hospital Clinical Research Funding (BJ-2022-195).

The authors declare that they have no competing interests.