Introduction Once-weekly subcutaneous semaglutide, 2.4 mg, a glucagon-like peptide-1 (GLP-1) receptor agonist (GLP-1RA), is available for weight management in people with obesity (or overweight and ≥1 weight-related comorbidities).1 It has demonstrated sustained, clinically meaningful reductions in body weight in people with overweight or obesity, with and without type 2 diabetes, in the ongoing global phase 3 Semaglutide Treatment Effect in People With Obesity (STEP) program.2-5 Semaglutide was the second GLP-1RA approved for weight management after once-daily subcutaneous liraglutide, 3.0 mg, which is available for chronic weight management in people with obesity (or overweight and ≥1 weight-related comorbidities).6 Semaglutide and liraglutide are modified, long-acting analogues of native GLP-1.7 Through addition of an albumin-binding C16 fatty acid side chain, liraglutide’s half-life is 13 to 15 hours. Semaglutide’s half-life is 165 hours, resulting from an amino acid replacement (preventing dipeptidyl peptidase 4 degradation) and a C18 fatty diacid addition.7,8 In a phase 2 trial, once-daily subcutaneous semaglutide, 0.4 mg (equivalent to 2.8 mg once weekly), significantly increased weight loss vs liraglutide, 3.0 mg.9 The STEP 8 trial directly compared once-weekly semaglutide, 2.4 mg, vs once-daily liraglutide, 3.0 mg, for weight management in adults with overweight or obesity to rigorously assess differences in efficacy and adverse event (AE) profiles.