Semaglutide
| Category | Metabolic & GLP-1 |
| Goals | Fat Loss |
| Evidence level | Approved (large Phase 3 RCTs; FDA-approved) |
| Legal status | Prescription drug — FDA-approved |
| FDA status | Ozempic (T2D, 2017); Rybelsus (oral, 2019); Wegovy (obesity, 2021; CV risk, 2024; MASH, Aug 2025); oral Wegovy 25 mg (obesity, Dec 2025) |
| Half-life | ~7 days (~160 h; once-weekly) |
| Routes | Subcutaneous · Oral |
| CAS / MW / Sequence | 910463-68-2 · ~4113.6 g/mol · GLP-1 analog (complex) |
| Last reviewed | 2026-06-07 |
In one line
A GLP-1 receptor agonist — the anchor GLP-1 brand — approved for type 2 diabetes, obesity, cardiovascular risk reduction, and (2025) MASH with liver fibrosis; now available as both a weekly injection and a daily pill.
Evidence at a glance
Semaglutide has extensive human evidence: the SUSTAIN (diabetes), STEP (obesity), and SELECT (cardiovascular) Phase 3 programs are large, randomized, placebo-controlled trials. It is FDA-approved as Ozempic, Rybelsus, and Wegovy. See Evidence Grading Explained and the Disclaimer.
Key Takeaways
- A GLP-1 receptor agonist — a GLP-1 analog with two amino-acid substitutions plus a fatty-diacid chain for once-weekly dosing.
- STEP obesity trials: ~12–15% mean body-weight reduction at the 2.4 mg dose; nearly two-thirds of patients lost ≥15% in some arms.
- SELECT trial: ~20% reduction in major adverse cardiovascular events in adults with established CVD and overweight/obesity.
- Available as subcutaneous (Ozempic, Wegovy) and oral (Rybelsus for T2D; oral Wegovy 25 mg for obesity, approved Dec 2025) formulations.
- In 2025 the FDA approved Wegovy for MASH with liver fibrosis (first GLP-1 for that use) and approved the oral Wegovy pill for weight management.
- The 2025 shortage resolution ended legal compounding of semaglutide copies (503A: Apr 22, 2025; 503B: May 22, 2025).
What Is It
Semaglutide is a GLP-1 analog — structurally based on human GLP-1 with two amino-acid substitutions (resisting DPP-4 degradation) and a C18 fatty-diacid chain that binds albumin to extend half-life to about a week. It is the active ingredient in Ozempic and Rybelsus (type 2 diabetes) and Wegovy (weight management; cardiovascular risk reduction), all made by Novo Nordisk. Development codes include NNC 0113-0217.
Mechanism of Action
Semaglutide is a GLP-1 receptor agonist (approved/clinical):
- Glucose-dependent insulin secretion — stimulates insulin release from pancreatic β-cells only when glucose is elevated, limiting hypoglycemia risk.
- Glucagon suppression — lowers hepatic glucose output.
- Slowed gastric emptying — prolongs satiety and blunts post-meal glucose spikes.
- Central appetite regulation — acts on hypothalamic and hindbrain GLP-1 receptors to reduce hunger and caloric intake.
One pathway, broad effects
Unlike the dual/triple agonists, semaglutide acts on a single incretin receptor (GLP-1). Its cardiovascular and renal benefits in trials suggest effects beyond glucose and weight alone.
Evidence by Outcome
| Outcome | Evidence | Notes |
|---|---|---|
| Weight loss (obesity) | Approved | STEP-1: ~14.9% mean loss at 2.4 mg over 68 wks vs ~2.4% placebo |
| Glycemic control (T2D) | Approved | SUSTAIN program; robust HbA1c reduction |
| Cardiovascular risk | Approved | SELECT: ~20% MACE reduction; FDA label expansion 2024 |
| Oral formulation efficacy | Approved | Rybelsus (oral, T2D); oral Wegovy 25 mg approved for obesity (Dec 2025, OASIS program) |
| Chronic kidney disease | Clinical | FLOW trial showed renal benefit in T2D with CKD |
| MASH / fatty liver | Approved | Accelerated approval Aug 2025 (Wegovy 2.4 mg) for MASH with moderate-to-advanced fibrosis; ESSENCE trial |
Reported Dosing
Not medical advice
The following reflects FDA-labeled titration. Dosing differs by indication and product, and must be individualized by a clinician. See Reconstitution & Dosing Math.
| Product / Goal | Titration | Maintenance | Notes |
|---|---|---|---|
| Wegovy (obesity, SC) | 0.25 → 0.5 → 1.0 → 1.7 → 2.4 mg, step every 4 wks | 2.4 mg weekly | Reaches target ~week 17 |
| Ozempic (T2D, SC) | 0.25 → 0.5 → 1.0 mg | up to 2.0 mg weekly | Start 0.25 mg (not therapeutic) |
| Rybelsus (T2D, oral) | 3 → 7 mg | up to 14 mg daily | Take fasting with small water; wait 30 min before eating |
Pharmacokinetics
Semaglutide has a half-life of ~7 days (~160 hours), enabling once-weekly subcutaneous dosing; steady state is reached in ~4–5 weeks. The oral form (Rybelsus) is co-formulated with the absorption enhancer SNAC and has low, variable bioavailability requiring strict fasting administration. See Half-Life & Pharmacokinetics.
Side Effects & Risks
- Gastrointestinal — nausea, vomiting, diarrhea, constipation; most common, dose-dependent, worst during escalation.
- Hypoglycemia — mainly when combined with insulin or sulfonylureas.
- Gallbladder disease, acute pancreatitis (rare), and acute kidney injury from dehydration secondary to severe GI symptoms.
- Boxed warning — thyroid C-cell tumor risk (rodent data); contraindicated with personal/family history of medullary thyroid carcinoma or MEN 2.
- Loss of lean mass with rapid weight loss; nutrition and resistance training commonly advised.
- Sourcing risk — gray-market “research” semaglutide is not quality-controlled. See Sourcing, Red Flags & Scams.
- See Side Effects & Risk Management and Bloodwork & Monitoring.
Cycling
There is no clinical concept of “cycling” semaglutide — it is a chronic maintenance therapy, and stopping typically leads to weight regain (as shown in the STEP-1 extension). Discontinuation should be managed clinically. See Cycling.
Stacks It Appears In
- Used as monotherapy in trials; in practice combined with diet, resistance training, and standard diabetes agents under medical supervision.
Comparisons
Sourcing & Quality
The only quality-assured semaglutide is the FDA-approved branded product (Ozempic/Wegovy/Rybelsus) via prescription. Following the 2025 shortage resolution, compounded versions are no longer broadly permitted. Gray-market lyophilized “research” semaglutide carries identity/purity risk — see How to Read a CoA, Red Flags & Scams. Reconstitution and storage: Reconstitution & Dosing Math, Storage & Handling. No vendors are endorsed here.
Legal & Regulatory Status
(As of 2026-06-07.) FDA-approved: Ozempic for type 2 diabetes (2017); Rybelsus oral for type 2 diabetes (2019); Wegovy for chronic weight management (approved 2021-06-04) with a 2024 label expansion to reduce cardiovascular risk in adults with established CVD and overweight/obesity (based on SELECT). In 2025 the FDA added two indications: Wegovy 2.4 mg injection for MASH (metabolic dysfunction-associated steatohepatitis) with moderate-to-advanced liver fibrosis (accelerated approval 2025-08-15; first GLP-1 for MASH), and oral Wegovy 25 mg for chronic weight management and cardiovascular risk reduction (approved 2025-12-22; first oral GLP-1 for weight loss). The FDA declared the semaglutide shortage resolved on Feb 21, 2025; enforcement deadlines ended legal compounding on Apr 22, 2025 (503A) and May 22, 2025 (503B). The FDA has proposed excluding semaglutide from the 503B Bulks List. See Regulatory & Legal Status.
FAQ
Is semaglutide FDA-approved? Yes — as Ozempic and Rybelsus (type 2 diabetes) and Wegovy (obesity; cardiovascular risk reduction; and, since Aug 2025, MASH with liver fibrosis).
How does it compare to tirzepatide? In SURMOUNT-5, tirzepatide produced greater weight loss than 2.4 mg semaglutide. See Semaglutide vs Tirzepatide.
Is there an oral version? Yes — Rybelsus is oral semaglutide for type 2 diabetes (taken fasting with a small sip of water). In December 2025 the FDA also approved oral Wegovy 25 mg, the first oral GLP-1 indicated for weight management (and cardiovascular risk reduction).
Can I still get compounded semaglutide? Broad legal compounding ended in mid-2025 after the shortage was resolved. Quality-assured product is the branded prescription drug.
References
- Wilding J.P.H. et al. (2021). “Once-Weekly Semaglutide in Adults with Overweight or Obesity” (STEP-1). New England Journal of Medicine.
- Marso S.P. et al. (2016). “Semaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes” (SUSTAIN-6). New England Journal of Medicine.
- Lincoff A.M. et al. (2023). “Semaglutide and Cardiovascular Outcomes in Obesity without Diabetes” (SELECT). New England Journal of Medicine.
- Perkovic V. et al. (2024). “Effects of Semaglutide on Chronic Kidney Disease in Patients with Type 2 Diabetes” (FLOW). New England Journal of Medicine.
- U.S. FDA approval records — Ozempic (2017), Rybelsus (2019), Wegovy (2021; CV expansion 2024); FDA statements on GLP-1 compounding wind-down (2025).
- U.S. FDA (2025-08-15). “FDA Approves Treatment for Serious Liver Disease Known as ‘MASH’.” fda.gov
- Novo Nordisk / FDA (2025-12-22). Oral Wegovy (semaglutide 25 mg) approval for chronic weight management (OASIS-4 program). FDA label (NDA 215256). accessdata.fda.gov
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