What is Semaglutide?
Semaglutide is a synthetic analog of GLP-1 (glucagon-like peptide-1), an intestinal hormone that the body naturally releases after eating. Developed by Novo Nordisk, it is the active ingredient in Ozempic (injectable, type 2 diabetes), Wegovy (injectable, obesity), and Rybelsus (oral, type 2 diabetes).
Unlike native GLP-1, which has a half-life of just 2 minutes, semaglutide has been molecularly modified to resist enzymatic degradation, achieving a half-life of ~7 days that allows weekly injection.
Mechanism of action
Semaglutide acts on GLP-1R receptors distributed in multiple tissues:
- Pancreas: Stimulates glucose-dependent insulin secretion and inhibits glucagon, reducing postprandial glucose without risk of severe fasting hypoglycemia.
- Hypothalamus: Acts on satiety centers, reducing appetite and caloric intake by an average of 20–35%.
- Stomach: Slows gastric emptying, prolonging the sensation of fullness.
- Liver: Reduces hepatic glucose production (gluconeogenesis).
- Heart: SUSTAIN and SELECT studies demonstrate reduction of major cardiovascular events (MACE) in high-risk patients.
Key clinical results
The STEP-1 trial (NEJM, 2021) showed average weight loss of 14.9% of body weight over 68 weeks with 2.4 mg/week vs. 2.4% with placebo. The SELECT trial (2023) reported a 20% reduction in MACE in obese patients without diabetes.
Dose escalation (approved protocol)
| Weeks | Weekly dose |
|---|---|
| 1–4 | 0.25 mg |
| 5–8 | 0.5 mg |
| 9–12 | 1.0 mg |
| 13–16 | 1.7 mg |
| 17+ | 2.4 mg (Wegovy) / 2.0 mg (Ozempic) |
Slow escalation minimizes nausea and gastrointestinal symptoms.
Frequent adverse effects
- Gastrointestinal (most common): nausea (44%), diarrhea (30%), vomiting (24%), constipation (24%) — generally transient and decrease over time.
- Hypoglycemia: Rare in monotherapy; greater risk when combined with sulfonylureas or insulin.
- Pancreatitis: Theoretically increased risk; contraindicated with personal/family history of pancreatitis.
- Thyroid: Contraindicated in medullary thyroid carcinoma or MEN2 (rodent data; human relevance uncertain).
- Gastroparesis: At high doses may excessively slow gastric emptying.
Important
Injectable semaglutide requires a medical prescription. “Research vials” are not the approved medication and are not subject to the same quality controls. This content is educational.
Always consult a licensed physician. FDA-approved semaglutide requires medical supervision and a valid prescription.
Reported protocol (research reference)
| Vial sizes | 5 mg, 10 mg, 20 mg |
|---|---|
| Reported dose | FDA-approved protocols start at 0.25 mg/week for 4 weeks, escalating to 2.4 mg/week (Wegovy) or 2.0 mg/week (Ozempic). Always under medical supervision. |
| Half-life | Approximately 7 days — allows weekly dosing. |
| FDA status | FDA approved |