Evidence Tier: FDA-Approved — Semaglutide is a GLP-1 receptor agonist approved by the FDA for type 2 diabetes (Ozempic/Rybelsus) and chronic weight management (Wegovy). One of the most extensively studied peptides in clinical medicine.
Overview
Semaglutide is a long-acting glucagon-like peptide-1 (GLP-1) receptor agonist developed by Novo Nordisk. It is 94% structurally homologous to native human GLP-1 with modifications that extend its half-life to approximately 7 days, allowing once-weekly dosing.
FDA-Approved Indications
- Ozempic (injectable): Type 2 diabetes mellitus
- Rybelsus (oral): Type 2 diabetes mellitus (first oral GLP-1 RA)
- Wegovy (injectable): Chronic weight management in adults with BMI ≥30 (or ≥27 with comorbidities)
Key Clinical Data
- STEP Trials (Weight): Mean weight loss of 14.9% at 68 weeks (STEP 1, n=1,961)
- SUSTAIN Trials (Diabetes): HbA1c reduction of 1.5-1.8% vs placebo
- SELECT Trial (Cardiovascular): 20% reduction in major adverse cardiovascular events (MACE) in overweight/obese adults without diabetes
Mechanism of Action
- Activates GLP-1 receptors in the pancreas, brain, gut, and cardiovascular system
- Enhances glucose-dependent insulin secretion from pancreatic beta cells
- Suppresses glucagon secretion
- Delays gastric emptying, promoting satiety
- Acts on hypothalamic appetite centers to reduce food intake
Compounding Status
Semaglutide has been available through 503A/503B compounding pharmacies during FDA-declared shortages. As of 2026, compounding restrictions are being revisited following shortage resolution. This remains a rapidly evolving regulatory area.
References
- Wilding JPH, et al. "Once-Weekly Semaglutide in Adults with Overweight or Obesity (STEP 1)." N Engl J Med. 2021;384(11):989-1002.
- Lincoff AM, et al. "Semaglutide and Cardiovascular Outcomes in Obesity without Diabetes (SELECT)." N Engl J Med. 2023;389(24):2221-2232.
- FDA Peptide Regulations 2026. PeptideLaws.com
Research Disclaimer
This article is compiled from peer-reviewed research and publicly available scientific literature. It is intended for educational and informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional before making health-related decisions.