Semaglutide Effects on Cardiovascular Outcomes in People With Overweight or Obesity (SELECT) rationale and design

Am Heart J. 2020 Nov;229:61-69. doi: 10.1016/j.ahj.2020.07.008. Epub 2020 Jul 17.

Abstract

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.

Publication types

  • Clinical Trial Protocol

MeSH terms

  • Cardiotonic Agents / administration & dosage
  • Cardiotonic Agents / adverse effects
  • Cardiovascular Diseases / epidemiology
  • Cardiovascular Diseases / prevention & control*
  • Clinical Trials, Phase III as Topic
  • Double-Blind Method
  • Female
  • Glucagon-Like Peptide 1 / agonists
  • Glucagon-Like Peptides* / administration & dosage
  • Glucagon-Like Peptides* / adverse effects
  • Heart Disease Risk Factors
  • Humans
  • Hypoglycemic Agents / administration & dosage
  • Hypoglycemic Agents / adverse effects
  • Male
  • Middle Aged
  • Obesity* / diagnosis
  • Obesity* / drug therapy
  • Obesity* / metabolism
  • Outcome Assessment, Health Care
  • Overweight* / diagnosis
  • Overweight* / drug therapy
  • Overweight* / metabolism
  • Randomized Controlled Trials as Topic
  • Weight Loss / drug effects*

Substances

  • Cardiotonic Agents
  • Hypoglycemic Agents
  • semaglutide
  • Glucagon-Like Peptides
  • Glucagon-Like Peptide 1