SEMAGLUTIDE

Phase 3 trials (SUSTAIN, PIONEER, STEP) demonstrate that semaglutide produces clinically significant weight loss of approximately 10-15% from baseline in both diabetic and non-diabetic populations, superior to placebo and other GLP-1 receptor agonists. The STEP 2 trial showed a -9.6% bodyweight reduction at 68 weeks with 2.4mg weekly dosing in patients with overweight/obesity and type 2 diabetes. A systematic review of non-diabetic obese patients found a mean weight reduction of -11.85% versus placebo. Safety data from extensive registration trials indicate mostly mild-to-moderate transient gastrointestinal adverse effects, though increased risk of cholelithiasis and acute pancreatitis has been observed. A 2024 retrospective cohort study suggested an association with nonarteritic anterior ischemic optic neuropathy (NAION), though causality has not been established. Evidence regarding impact on lean body mass remains insufficient, with some studies suggesting a proportional loss of lean mass alongside fat mass.