Diabetes Dialogue: SELECT, Semaglutide, & the Future of Incretin Therapies, with A. Michael Lincoff, MD

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In this episode, hosts are joined by co-chair of the SELECT steering committee A. Michael Lincoff, MD, to discuss results, potential explanations for cardiovascular benefit beyond weight reduction, FLOW trial implications, and the future of incretin therapies.

Key Timestamps & Highlights

00:40 - Guest Introduction

01:15 - SELECT Results Overview

04:30 - Next Steps for Research

07:20 - Mechanism of Action for CV Benefit

09:05 - FLOW Trial Implications

11:30 - Impact on Access

15:05 - Future of Incretin Therapies

21:50 - Predicting the Next 5-10 Years for Semaglutide

Excitement and popularity of GLP-1 receptor agonists has snowballed in the last half decade, driven primarily by the revelations of the weight loss benefits seen with semaglutide.

However, even with all the praise and demonstrated benefits on glycemic control and chronic weight management, many questions regarding the potential cardiovascular benefit of the agent remained unanswered. That is, until the announcement and subsequent presentation of results from the landmark SELECT trial, which was presented at the American Heart Association 2023 Scientific Sessions.

A 17,000-patient, multicenter, double-blind, randomized, placebo-controlled, event-driven superiority trial, SELECT compared semaglutide 2.4 mg (Wegovy) against placebo therapy as adjuncts to optimal lifestyle management in people with obesity or overweight plus 1 weight-related comorbidity without type 2 diabetes. The largest and longest trial of semaglutide in adults without type 1 or type 2 diabetes, the trial’s primary outcome of interest was a composite of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke in a time-to-first-event analysis.

Results of the study suggested a primary outcome event occurred among 6.5% of the semaglutide 2.4 mg group and 8.0% of the placebo group (HR, 0.80; 95% Confidence interval [CI], 0.72 to 0.90; P <.001). Analysis of secondary outcomes provided evidence of nonsignificant trends towards benefit for cardiovascular death (HR, 0.85; 95% CI, 0.71 to 1.01; P=.07), heart failure hospitalization or urgent medical visit (HR, 0.82; 95% CI, 0.71 to 0.96), all-cause mortality (HR, 0.81; 95% CI, 0.71 to 0.93), an HbA1c of 6.5% or greater (HR, 0.27; 95% CI, 0.24 to 0.31).

Following presentation at AHA 2023, much of the discussion surrounding the trial focused on the early separation of event curves observed with use of semaglutide, which would suggest the cardiovascular benefit observed for the primary outcome was not driven entirely by reductions in body weight.

In this episode of Diabetes Dialogue: Technology, Therapeutics, & Real-World Perspectiveshosts Diana Isaacs, PharmD, an endocrine clinical pharmacist, director of Education and Training in Diabetes Technology, and codirector of Endocrine Disorders in Pregnancy at the Cleveland Clinic, and Natalie Bellini, DNP, program director of Diabetes Technology at University Hospitals Diabetes and Metabolic Care Center, are joined by co-chair of the SELECT steering committee A. Michael Lincoff, MD, who serves vice chairman of the Robert and Suzanne Tomsich Department of Cardiovascular Medicine and an interventional cardiologist in the Sydell and Arnold Miller Family Heart, Vascular & Thoracic Institute at Cleveland Clinic. During the episode, Lincoff offers hosts insight into the SELECT results, potential explanations for cardiovascular benefit beyond weight reduction, FLOW trials implications, and the future of incretin therapies.

Relevant disclosures for Dr. Lincoff include Novo Nordisk, Eli Lilly and Company, Esperion, Novartis, Ardelyx, and others. Relevant disclosures for Dr. Isaacs include Eli Lilly and Company, Novo Nordisk, Sanofi, Abbott Diabetes Care, Dexcom, Medtronic, and others. Relevant disclosures for Dr. Bellini include Abbott Diabetes Care, MannKind, Provention Bio, and others.

References:

  1. Campbell P. Semaglutide 2.4 mg (Wegovy) reduces cardiovascular risk in overweight/obesity with CVD. HCP Live. November 11, 2023. Accessed March 2, 2024. https://www.hcplive.com/view/semaglutide-2-4-mg-wegovy-reduces-cardiovascular-risk-in-overweight-obesity-with-cvd.
  2. Vaduganathan M, Greene SJ. Don’t miss a beat: Select, Dapa-mi, & aha 2023. HCP Live. November 15, 2023. Accessed March 2, 2024. https://www.hcplive.com/view/dont-miss-a-beat-select-dapa-mi-aha-2023.
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