Semaglutide
GLP-1 Receptor AgonistFDA-approvedAlso known as: Ozempic, Wegovy, Rybelsus, NN9535
An FDA-approved GLP-1 receptor agonist used for type 2 diabetes and chronic weight management, producing significant weight loss of 15-17% body weight in clinical trials.
Overview
Semaglutide is a long-acting glucagon-like peptide-1 (GLP-1) receptor agonist originally developed by Novo Nordisk for type 2 diabetes (marketed as Ozempic) and later approved at a higher dose for chronic weight management (Wegovy). It is a modified analog of human GLP-1 with 94% structural homology, engineered with key amino acid substitutions and a fatty acid side chain that dramatically extends its half-life to approximately 7 days, allowing once-weekly dosing. Semaglutide has become one of the most prescribed and culturally prominent peptide drugs in history, catalyzing the 'GLP-1 revolution' in obesity treatment. Beyond weight loss and glycemic control, emerging research suggests cardiovascular benefits, potential neuroprotective effects, and applications in addiction, liver disease (MASH/NASH), and kidney disease. An oral formulation (Rybelsus) is also available, making it one of the first oral peptide drugs.
Mechanism of Action
Semaglutide mimics the incretin hormone GLP-1, acting through multiple mechanisms: (1) Stimulates glucose-dependent insulin secretion from pancreatic beta cells, lowering blood sugar only when glucose is elevated; (2) Suppresses glucagon secretion, reducing hepatic glucose output; (3) Slows gastric emptying, prolonging satiety after meals; (4) Acts on hypothalamic GLP-1 receptors to reduce appetite and food intake centrally; (5) May improve beta-cell function and survival over time; (6) Reduces cardiovascular inflammation and atherosclerosis markers; (7) Emerging evidence for direct effects on reward circuitry in the brain, potentially reducing cravings for food and addictive substances.
Molecular Formula
C187H291N45O59
Molecular Weight
4113.58 g/mol
Sequence
Modified GLP-1 analog (His-Aib-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Lys(C18 fatty diacid)-Glu-Phe-Ile-Ala-Trp-Leu-Val-Arg-Gly-Arg-Gly)
Dosage Protocols
Dose Range
0.25mg – 2mg
Frequency
Once weekly
Route
subcutaneous
Cycle Length
Ongoing (chronic therapy)
Start at 0.25mg for 4 weeks, escalate to 0.5mg, then optionally to 1mg or 2mg. Inject in abdomen, thigh, or upper arm. Rotate injection sites.
Source: FDA prescribing information (Ozempic)
Side Effects
| Effect | Severity |
|---|---|
| Nausea | moderate |
| Vomiting | moderate |
| Diarrhea | mild |
| Constipation | mild |
| Injection site reactions | mild |
| Pancreatitis | severe |
| Gallbladder events | severe |
| Thyroid C-cell tumors | severe |
| Muscle loss | moderate |
| Gastroparesis | moderate |
Pros & Cons
Produces the most significant weight loss of any approved pharmaceutical — average 15-17% body weight reduction
FDA-approved with extensive Phase 3 clinical trial data (STEP and SUSTAIN programs) in thousands of patients
Proven cardiovascular benefits — reduced MACE events by 20% in the SELECT trial
Once-weekly dosing provides excellent convenience and adherence
Dual benefits for weight loss and blood sugar control in diabetic patients
Significant GI side effects (nausea, vomiting) especially during dose escalation, causing ~7% discontinuation rate
Weight regain is common after discontinuation — two-thirds of lost weight may return within a year
High cost without insurance ($1,000-1,300/month) and frequent insurance coverage issues for weight loss indication
Loss of lean muscle mass alongside fat, requiring deliberate resistance training to mitigate
Supply shortages have been persistent since 2022 due to overwhelming demand
Research Studies
Legal Status
FDA-approved for type 2 diabetes (Ozempic, 2017) and chronic weight management (Wegovy, 2021). Prescription required. Available as oral formulation (Rybelsus). Covered by many insurance plans for diabetes; weight loss coverage varies.
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