FDA-Regulated Compound
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Semaglutide
Ozempic / Wegovy / Rybelsus
Semaglutide is an FDA-approved GLP-1 receptor agonist originally developed by Novo Nordisk for type 2 diabetes (Ozempic, Rybelsus) and later approved for chronic weight management (Wegovy). It is a 31-amino acid peptide analog of human GLP-1 with a half-life of approximately 7 days, enabling once-weekly dosing. It has become one of the most commercially successful peptide drugs in history, with combined annual revenues exceeding $20 billion.
Mechanism of Action
GLP-1 receptor agonist that mimics incretin hormones. Enhances insulin secretion in a glucose-dependent manner, suppresses glucagon release, and slows gastric emptying. Centrally reduces appetite through hypothalamic signaling.
Research Protocols
For research purposes only. Not medical advice.
Typical research protocols use 0.25mg weekly for 4 weeks, escalating to 0.5mg weekly, then 1mg weekly. Maximum studied dose is 2.4mg weekly for weight management.
Research Notes
Clinical Research Status
FDA-approved for type 2 diabetes (Ozempic 2017, Rybelsus 2019) and obesity (Wegovy 2021). Ongoing Phase 3 trials for NASH/MASH (liver disease), heart failure with preserved ejection fraction, Alzheimer's disease, and substance use disorders. SELECT trial demonstrated 20% cardiovascular risk reduction in overweight patients.
Key Published Findings
STEP trials demonstrated 15-17% average body weight loss over 68 weeks at 2.4mg weekly dose. SUSTAIN trials showed HbA1c reductions of 1.5-1.8% in type 2 diabetes. PIONEER trials established efficacy of oral formulation. FLOW trial showed 24% reduction in kidney disease progression. STEP HFpEF trial showed significant improvement in heart failure symptoms and physical limitations.
Safety Profile
Most common side effects are gastrointestinal: nausea (40-44%), diarrhea (30%), vomiting (24%), constipation (24%). These typically diminish with dose titration. Black box warning for thyroid C-cell tumors (observed in rodents, not confirmed in humans). Reports of pancreatitis, gallbladder events, and retinopathy complications. Post-marketing reports of suicidal ideation under investigation.
Drug Interactions & Contraindications
Contraindicated in patients with personal/family history of medullary thyroid carcinoma or MEN2 syndrome. Delays gastric emptying, which may affect absorption of other oral medications. Caution with insulin or sulfonylureas (increased hypoglycemia risk). Not recommended during pregnancy or breastfeeding.
Comparison to Related Compounds
More potent and longer-acting than liraglutide (Victoza/Saxenda). Tirzepatide (Mounjaro/Zepbound) is a dual GIP/GLP-1 agonist showing slightly greater weight loss (up to 22.5% in SURMOUNT trials). Retatrutide (triple agonist) in Phase 3 trials shows even greater efficacy. CagriSema (semaglutide + cagrilintide) in Phase 3 trials combines GLP-1 and amylin pathways.
Community Observations
Extreme demand has led to widespread shortages and compounding pharmacy versions of varying quality. Counterfeit products are a significant concern. Users commonly report dramatic appetite suppression, food noise reduction, and altered relationship with alcohol. Muscle loss during weight loss is a frequently discussed concern — resistance training and adequate protein intake are widely recommended.
Half-Life
~7 days
Reconstitution
Bacteriostatic water (BAC)
Storage
Lyophilized
Room temperature up to 36 months. Protect from light.
Reconstituted
Refrigerate 2-8C. Use within 56 days.
US Legal Status
Also Known As
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