Once-weekly semaglutide 2.4 mg plus lifestyle intervention produced 14.9% mean weight loss vs 2.4% with placebo at 68 weeks in adults with obesity/overweight without diabetes.
1,961 adults, BMI >=30 (or >=27 with comorbidity), STEP 1
Semaglutide
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Metabolic
Semaglutide
A GLP-1 medicine for type 2 diabetes and weight management
FDA-approved · by prescriptionFDA-approved as Ozempic, Rybelsus and Wegovy for type 2 diabetes and chronic weight management, among other indications.
Consultations are opening state by state.
Boxed warningRisk of thyroid C-cell tumors: semaglutide caused thyroid C-cell tumors in rodents, and whether it does so in humans is unknown. It is contraindicated in people with a personal or family history of medullary thyroid carcinoma (MTC) or multiple endocrine neoplasia syndrome type 2 (MEN 2).
Overview.
Semaglutide is a GLP-1 receptor agonist given as a once-weekly injection or a once-daily tablet. In the US it is approved for type 2 diabetes (Ozempic injection; Rybelsus and Ozempic tablets), including cardiovascular and kidney risk reduction, and for chronic weight management, cardiovascular risk reduction and MASH (Wegovy injection; Wegovy tablets approved Dec 2025). It anchored a 2022-2025 US supply shortage that reshaped compounding-pharmacy regulation. It is a modified 31-amino-acid analog of human GLP-1 with a fatty-acid chain that extends its half-life to about a week.
Also known as Ozempic · Wegovy · Rybelsus
The molecule, decoded.
- Sequence
-
H-[Aib]-EGTFTSDVSSYLEGQAAKEFIAWLVRGRG (31 aa, GLP-1(7-37) backbone)
- Length
- 31 residues
- Molecular weight
- 4,114 g/mol
- Formula
- C187H291N45O59
- CAS number
- 910463-68-2
- Half-life
- ~1 week (allows once-weekly injection)
- Routes studied
- subcutaneous injection, oral tablet (with the SNAC absorption enhancer; lower, variable absorption, so taken daily)
- Modifications
- Aib (2-aminoisobutyric acid) at position 2 (position 8 in GLP-1 numbering) for DPP-4 resistance; arginine at position 28 (Arg34 in GLP-1 numbering) in place of lysine, so only one fatty acid can attach; lysine 20 (Lys26 in GLP-1 numbering) linked via two AEEA (mini-PEG) spacers and a gamma-Glu linker to a C18 fatty diacid for albumin binding; C-terminal free acid
How it works.
Semaglutide activates the GLP-1 receptor on pancreatic beta cells, stimulating glucose-dependent insulin secretion and suppressing glucagon release, which lowers blood glucose. It also acts on GLP-1 receptors in the hypothalamus and brainstem to reduce appetite and slow gastric emptying, producing sustained caloric-intake reduction and weight loss.
Evidence · FDA-approved · regulatory-grade trials
What the research shows
In SURPASS-2, semaglutide 1 mg was compared head-to-head against tirzepatide; tirzepatide produced greater A1c and weight reductions, establishing semaglutide's relative efficacy benchmark in T2D.
adults with type 2 diabetes on metformin
FDA declared the national injectable semaglutide (Ozempic/Wegovy) shortage resolved, ending a nearly three-year shortage that had permitted broad 503A/503B compounding.
US drug supply, all presentations
FDA warned that compounded products using semaglutide salt forms (semaglutide sodium, semaglutide acetate) are different active ingredients that have not been shown to be safe or effective.
n/a - regulatory safety communication
FDA proposed excluding semaglutide (with tirzepatide and liraglutide) from the 503B bulks list, finding no clinical need for outsourcing facilities to compound it from bulk substance once approved products are available.
n/a - rulemaking
What to know first.
Based on: the FDA-approved label.
Boxed warningRisk of thyroid C-cell tumors: semaglutide caused thyroid C-cell tumors in rodents, and whether it does so in humans is unknown. It is contraindicated in people with a personal or family history of medullary thyroid carcinoma (MTC) or multiple endocrine neoplasia syndrome type 2 (MEN 2).
Reported side effects
- nausea
- vomiting
- diarrhea
- constipation
- abdominal pain
Cautions
- Boxed warning: thyroid C-cell tumors in rodents (human relevance unknown); contraindicated with personal/family history of medullary thyroid carcinoma or MEN 2
- acute pancreatitis
- acute gallbladder disease
- acute kidney injury due to volume depletion
- severe gastrointestinal adverse reactions; not recommended in severe gastroparesis
- hypersensitivity reactions (anaphylaxis, angioedema)
- diabetic retinopathy complications in patients with type 2 diabetes
- heart rate increase (Wegovy)
- pulmonary aspiration during general anesthesia or deep sedation
- hypoglycemia risk when combined with insulin/sulfonylureas
Checked 2026-09
Where it stands.
FDA-approved, by prescription.
Approved use. Semaglutide is FDA-approved as Ozempic injection and as Rybelsus and Ozempic tablets for type 2 diabetes, including lowering the risk of major cardiovascular events (and, for Ozempic injection, of kidney-disease progression) in certain patients, and as Wegovy injection and tablets for chronic weight management and for lowering major cardiovascular event risk in certain adults; Wegovy injection is also approved for weight management in adolescents 12 and older with obesity and, under accelerated approval, for noncirrhotic MASH with F2-F3 liver fibrosis.
When consultations open, a licensed clinician in your state will review your health history and prescribe Semaglutide only if it’s appropriate for you. A licensed U.S. pharmacy will dispense it.
- FDA
- approved: Ozempic injection (2017; T2D glycemic control, MACE risk reduction in T2D with established CVD, kidney-outcome risk reduction in T2D with CKD added Jan 2025); Rybelsus tablets (2019; T2D glycemic control, MACE risk reduction in high-risk T2D added Oct 2025; the newer R2 tablet formulation was renamed 'Ozempic tablets' in Jan 2026); Wegovy injection (2021; chronic weight management in adults and adolescents 12+, MACE risk reduction added Mar 2024, noncirrhotic MASH with F2-F3 fibrosis under accelerated approval added Aug 2025, 7.2 mg dose added Mar 2026); Wegovy tablets 25 mg (approved Dec 22, 2025; weight management and MACE risk reduction in adults)
- Approved products
- Ozempic (FDA, 2017): type 2 diabetes glycemic control; MACE risk reduction in T2D with established CVD; reduce risk of eGFR decline, ESKD and CV death in T2D with CKD Label
- Rybelsus (and Ozempic tablets, renamed R2 formulation) (FDA, 2019): type 2 diabetes glycemic control (oral); MACE risk reduction in adults with T2D at high CV risk Label
- Wegovy (injection) (FDA, 2021): chronic weight management (adults; adolescents 12+ with obesity); MACE risk reduction in adults with CVD and obesity/overweight; noncirrhotic MASH with F2-F3 fibrosis (accelerated approval) Label
- Wegovy (tablets) (FDA, 2025): chronic weight management and MACE risk reduction in adults (25 mg once daily) Label
- Compounding
- Shortage (Mar/Aug 2022 - Feb 2025) let 503A/503B compounders make 'essentially a copy' under FDCA exceptions. FDA declared the shortage resolved Feb 21, 2025; 503A enforcement discretion ran to Apr 22, 2025 and 503B to May 22, 2025. On Apr 30, 2026 FDA proposed NOT to include semaglutide on the 503B bulks list (91 FR 23431; comment period extended to Jul 30, 2026 by 2026-12937); no final determination as of Sep 2026. Compounding under 503A remains possible only for products that are not 'essentially a copy' of an approved drug (e.g., a documented patient-specific change).
- Sport (WADA)
- Not on the WADA Prohibited List; added to the WADA 2026 Monitoring Program (monitored, not sanctioned) starting 2024, and WADA's Executive Committee confirmed GLP-1 receptor agonists will not be added to the 2027 Prohibited List.
- Enforcement
- FDA safety communication on illegal semaglutide salt compounding (semaglutide sodium/acetate) (2023)
- FDA alert on dosing errors with compounded injectable semaglutide (Jul 2024)
- FDA proposed NOT to include semaglutide on the 503B bulks list (Apr 30, 2026; comments extended to Jul 30, 2026; final determination pending)