Semaglutide
Summary
Semaglutide is a GLP-1 receptor agonist peptide with strong trial evidence for weight loss: STEP-1 showed ~15% mean weight reduction over 68 weeks, and the SELECT trial demonstrated cardiovascular benefit in obesity without diabetes. It is FDA-approved for weight management (Wegovy) and type 2 diabetes (Ozempic).
Mechanism
Semaglutide is a GLP-1 (glucagon-like peptide-1) receptor agonist, a modified human GLP-1 analog with an attached fatty-acid chain that extends its half-life to about a week. It slows gastric emptying, stimulates glucose-dependent insulin release, suppresses glucagon, and acts on hypothalamic appetite circuits to reduce hunger and energy intake.
Reported effects
Ratings are relative to peers in the same category, not absolute claims.
Studied dosing — research context
In STEP-1, participants received 2.4 mg subcutaneously once weekly for 68 weeks, with a 16-week dose-escalation period, alongside lifestyle intervention. Mean weight change was -14.9% vs -2.4% with placebo. FDA-approved (Wegovy) for chronic weight management in adults and adolescents with obesity. This describes research protocols, not guidance.
Research context only. This is not a recommendation.
Safety
Gastrointestinal events (nausea, diarrhea, vomiting, constipation) are the most common adverse effects, typically transient and mild to moderate. It carries a boxed warning for thyroid C-cell tumors seen in rodents (human relevance unknown) and is contraindicated with a personal or family history of medullary thyroid carcinoma or MEN 2. Pancreatitis and gallbladder disease have been reported; not recommended in pregnancy.
Limitations
Trial populations were adults with overweight or obesity; effects in other groups are less studied. Weight regain after stopping is substantial, suggesting chronic use is needed to maintain benefit. Long-term (decade-scale) safety data are still being collected.