American heart journalSep 11, 2020

How Semaglutide May Affect Heart Health in People with Overweight or Obesity: Study Plan

GLP-1 Therapies Weekly Brief ↗PubMed ↗DOI ↗

Updated Mar 28, 2026

Abstract

The GLP-1 receptor agonist semaglutide is being evaluated in a phase 3 trial for its ability to reduce major adverse cardiovascular events in patients with overweight or obesity and established cardiovascular disease.

Obesity is recognized as a significant risk factor for cardiovascular disease.
Current treatments for cardiovascular risk primarily focus on managing lipids, blood pressure, and other related conditions rather than weight loss.
GLP-1 receptor agonists, including semaglutide, are associated with weight reduction and improved blood sugar levels.
Semaglutide is being tested against a placebo to determine its effectiveness in preventing cardiovascular events in a specific high-risk population.
SELECT is the first trial to investigate whether an antiobesity medication can significantly reduce cardiovascular events in patients without diabetes.

Simplified

Cardiovascular disease (CVD) is a major cause of morbidity and mortality. Although it has been widely appreciated that obesity is a major risk factor for CVD, treatments that produce effective, durable weight loss and the impact of weight reduction in reducing cardiovascular risk have been elusive. Instead, progress in CVD risk reduction has been achieved through medications indicated for controlling lipids, hyperglycemia, blood pressure, heart failure, inflammation, and/or thrombosis. Obesity has been implicated as promoting all these issues, suggesting that sustained, effective weight loss may have independent cardiovascular benefit. GLP-1 receptor agonists (RAs) reduce weight, improve glycemia, decrease cardiovascular events in those with diabetes, and may have additional cardioprotective effects. The GLP-1 RA semaglutide is in phase 3 studies as a medication for obesity treatment at a dose of 2.4 mg subcutaneously (s.c.) once weekly. Semaglutide Effects on Heart Disease and Stroke in Patients with Overweight or Obesity (SELECT) is a randomized, double-blind, parallel-group trial testing if semaglutide 2.4 mg subcutaneously once weekly is superior to placebo when added to standard of care for preventing major adverse cardiovascular events in patients with established CVD and overweight or obesity but without diabetes. SELECT is the first cardiovascular outcomes trial to evaluate superiority in major adverse cardiovascular events reduction for an antiobesity medication in such a population. As such, SELECT has the potential for advancing new approaches to CVD risk reduction while targeting obesity.

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How Semaglutide May Affect Heart Health in People with Overweight or Obesity: Study Plan

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