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

• Published in: The American heart journal 2020-11, Vol.229, p.61-69
• Main Authors: Ryan, Donna H., Lingvay, Ildiko, Colhoun, Helen M., Deanfield, John, Emerson, Scott S., Kahn, Steven E., Kushner, Robert F., Marso, Steve, Plutzky, Jorge, Brown-Frandsen, Kirstine, Gronning, Marianne O.L., Hovingh, G. Kees, Holst, Anders Gaarsdal, Ravn, Henrik, Lincoff, A. Michael
• Format: Article
• Language: English
• Subjects: Angina pectoris; Antidiabetics; Blood glucose; Blood pressure; Body weight; Body weight loss; Cardiotonic Agents - administration & dosage; Cardiotonic Agents - adverse effects; Cardiovascular disease; Cardiovascular diseases; Cardiovascular Diseases - epidemiology; Cardiovascular Diseases - prevention & control; Clinical Trials, Phase III as Topic; Congestive heart failure; Coronary artery disease; Diabetes; Diabetes mellitus; Double-Blind Method; Female; GLP-1 receptor agonists; Glucagon; Glucagon-Like Peptide 1 - agonists; Glucagon-Like Peptides - administration & dosage; Glucagon-Like Peptides - adverse effects; Health risks; Heart Disease Risk Factors; Heart diseases; Humans; Hyperglycemia; Hypoglycemic Agents - administration & dosage; Hypoglycemic Agents - adverse effects; Lipids; Male; Metabolism; Middle Aged; Morbidity; Obesity; Obesity - diagnosis; Obesity - drug therapy; Obesity - metabolism; Outcome Assessment, Health Care; Overweight; Overweight - diagnosis; Overweight - drug therapy; Overweight - metabolism; Randomized Controlled Trials as Topic; Risk analysis; Risk factors; Risk management; Stroke; Thromboembolism; Thrombosis; Weight control; Weight loss; Weight Loss - drug effects; Weight reduction
• ISSN: 0002-8703; 1097-6744
• DOI: 10.1016/j.ahj.2020.07.008

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.