Role of Incretin-Based Therapies in Obesity Management

Mechanism of Action and Clinical Efficacy

GLP-1 receptor agonists are highly effective for obesity management, producing significant weight loss of 6.1-17.4% in non-diabetic individuals, with semaglutide and tirzepatide showing the greatest efficacy comparable to bariatric surgery, according to the American College of Cardiology 1, 2
GLP-1 receptor agonists work through multiple mechanisms to promote weight loss, including inhibition of appetite and increased satiety through central actions on the hypothalamus and brainstem nuclei, as recommended by the American Heart Association 3, 2

Beyond weight loss, GLP-1 receptor agonists provide significant cardiometabolic benefits, including reduced risk of cardiovascular events in patients with or without diabetes, improved heart failure symptoms in patients with preserved ejection fraction, and beneficial effects on blood pressure and lipid profiles, as stated by the American Diabetes Association 1, 2
The American College of Cardiology recommends semaglutide for reducing cardiovascular events in non-diabetic patients with obesity and established cardiovascular disease, with a hazard ratio of 0.80 2

Common adverse effects of GLP-1 receptor agonists include nausea and vomiting, dyspepsia and gastrointestinal reflux, diarrhea or constipation, and gallbladder disorders, as reported by the National Institute of Diabetes and Digestive and Kidney Diseases 1, 5
The American Society of Anesthesiologists suggests considering delayed gastric emptying when using GLP-1 receptor agonists in perioperative settings, with increased risk of pulmonary aspiration during anesthesia 6, 8

For patients with BMI ≥30 or BMI ≥27 with weight-related complications, the American Heart Association recommends starting with lower doses and titrating upward slowly to minimize gastrointestinal side effects, combining with lifestyle modifications, and monitoring for improvement in weight and comorbidities 2
The Endocrine Society suggests avoiding GLP-1 receptor agonists in patients with gastroparesis and using with caution in patients requiring anesthesia due to delayed gastric emptying 1, 6, 8