Semaglutide

Semaglutide is best known as the medicine behind Ozempic and Wegovy — a GLP-1 receptor agonist that copies a natural gut hormone involved in fullness and blood-sugar control. It's an FDA-approved prescription medicine, sold as Ozempic for type 2 diabetes and Wegovy for weight management, as a weekly injection under the skin or a daily tablet. In the US, the Ozempic tablet replaced Rybelsus in 2026; Rybelsus is still the name elsewhere.

Semaglutide (Ozempic, Wegovy) is a GLP-1 injection with the deepest evidence base in its class, FDA-approved for type 2 diabetes and weight management. In large trials it lowered blood sugar (HbA1c) and, at higher doses, produced average weight loss of about 15% over 68 weeks versus about 2% on placebo. A separate outcomes trial reported a 20% reduction in major heart events in adults with overweight or obesity and existing heart disease. In the ESSENCE trial in fatty-liver disease (MASH), more participants had resolution of steatohepatitis without worsening fibrosis than on placebo (62.9% vs 34.3%), and in the FLOW trial (type 2 diabetes with chronic kidney disease) it reduced a composite of kidney and cardiovascular events (hazard ratio 0.76). It has the longest safety record of the GLP-1 family. The research attributes these weight and blood-sugar changes largely to reduced appetite and food intake (greater satiety via the gut-hormone pathway these agents act on), an appetite and energy-intake mechanism measured across the trials.

FDA approved across multiple brands and indications — Ozempic (type 2 diabetes, 2017; cardiovascular risk reduction, 2020; chronic kidney disease progression, Jan 2025 on the FLOW trial); Wegovy (chronic weight management, 2021; cardiovascular risk reduction, 2024 on the SELECT trial; noncirrhotic MASH with moderate-to-advanced fibrosis, accelerated approval Aug 2025 on the ESSENCE trial); Rybelsus (oral, type 2 diabetes, 2019; cardiovascular risk reduction, Oct 2025 on the SOUL trial; sold in the US as Ozempic tablets since May 2026). The Wegovy pill (once-daily oral semaglutide) was approved in Dec 2025 for weight reduction and cardiovascular risk reduction. A peripheral artery disease label update (STRIDE trial) is approved in the EU but, as of September 2026, not by the FDA.

Semaglutide is a prescription-only medication. VialWise is a research and educational reference, not medical advice — talk to a licensed clinician before considering any compound.

⚠️ Semaglutide is FDA approved under several brand names (Ozempic, Wegovy, Rybelsus) for specific indications. Information in this entry is informational, not medical advice. Always confirm dose calculations with the in-app calculator and consult appropriate professional guidance before any protocol decisions.

⚠️ Precision matters at low doses. Small dosing errors that look trivial in absolute terms can be significant in percentage terms when starting doses are small. A one-unit mis-draw at a 5-unit dose is a 20% error; the same one-unit error at a 50-unit dose is only 2%. This applies most acutely to semaglutide's starting dose, which lands depending on reconstitution. Always verify draws against the in-app calculator and double-check the unit count on the syringe before injecting.

Semaglutide is a glucagon-like peptide-1 (GLP-1) receptor agonist developed by Novo Nordisk and marketed under brand names that depend on indication and route: Ozempic for type 2 diabetes (weekly injection, and in the US since May 2026 a daily tablet), Wegovy for weight management (weekly injection or daily tablet), and Rybelsus, the original daily tablet for type 2 diabetes, which keeps that name outside the US.[¹⁶] Its approved indications have expanded well beyond glucose and weight control. Ozempic added cardiovascular risk reduction (2020) and, on the basis of the phase-3b FLOW trial, reduction in the risk of sustained kidney-function decline, end-stage kidney disease and cardiovascular death in adults with type 2 diabetes and chronic kidney disease (FDA approved January 2025).[¹⁰] Wegovy added cardiovascular risk reduction (March 2024, on the SELECT trial[²][¹⁴]) and, on the basis of the phase-3 ESSENCE trial, treatment of noncirrhotic MASH with moderate-to-advanced liver fibrosis (accelerated approval August 2025; Novo Nordisk describes it as the first GLP-1 approved for MASH).[⁹] Rybelsus added reduction of major cardiovascular events in adults with type 2 diabetes at high risk, on the basis of the phase-3b SOUL trial (FDA approved October 2025; at the time, the only oral GLP-1 with a cardiovascular indication).[¹¹] In the US that tablet has since been reformulated and renamed: since May 2026 it is sold as Ozempic tablets.[¹⁶] A once-daily semaglutide tablet, the Wegovy pill, was approved in December 2025 to reduce excess body weight and keep it off long term, and to reduce cardiovascular risk.[¹⁵] A peripheral-artery-disease label update based on the phase-3b STRIDE trial was approved in the EU in 2025; Novo Nordisk filed for the same update in the US, but as of September 2026 it is not an FDA-approved indication.[¹²] (Note: in two phase-3 trials in early Alzheimer's disease, evoke and evoke+, oral semaglutide did not slow clinical progression compared with placebo; the planned extension periods were stopped and both trials were discontinued. Semaglutide has no established role in Alzheimer's disease or other neurodegenerative conditions.[¹³]) It is the most extensively studied incretin therapy currently approved, with millions of patient-years of post-marketing data and several large cardiovascular outcomes trials supporting its safety and efficacy in defined populations.

Mechanistically, semaglutide is a single-receptor agonist (GLP-1 only) — distinct from the dual agonist tirzepatide (GLP-1/GIP) and the triple agonist retatrutide (GLP-1/GIP/glucagon). GLP-1 receptor activation drives glucose-dependent insulin secretion, suppresses glucagon, slows gastric emptying, and reduces appetite through central pathways acting on the arcuate nucleus of the hypothalamus. The 39-amino-acid peptide is conjugated to a C18 fatty di-acid moiety for albumin binding, which is the structural basis for once-weekly subcutaneous dosing;[⁵] the human elimination half-life of approximately 1 week is the value reported in the FDA prescribing information.[⁶]

The pivotal obesity trial (STEP-1; Wilding et al., NEJM 2021; n=1,961) reported a least-squares mean weight reduction of −14.9% with semaglutide weekly versus −2.4% with placebo at 68 weeks, when combined with lifestyle intervention.[¹] In type 2 diabetes, trials across the SUSTAIN program reported HbA1c reductions of approximately 1.0–1.8 percentage points with weight reductions of several kilograms; the specific trial cited here — SUSTAIN-6 — was a cardiovascular-safety trial at the and weekly doses (the weekly Ozempic dose derives from the later sustain FORTE trial, not cited).[³] The SELECT cardiovascular outcomes trial (Lincoff et al., NEJM 2023; n=17,604) reported a 20% reduction in major adverse cardiovascular events in adults with overweight or obesity and pre-existing cardiovascular disease but without diabetes — the first GLP-1 trial to show CV benefit independent of diabetes status.[²]

Semaglutide differs from retatrutide and tirzepatide in three respects worth flagging for researchers comparing the GLP-1 family: (1) lower absolute weight loss in head-to-head and cross-trial comparisons (~15% vs ~21% for tirzepatide vs ~25–28% for retatrutide at maximum doses, the retatrutide figure reflecting its phase-3 read-out); (2) the longest published safety record by a wide margin; and (3) the only GLP-1 with established cardiovascular outcomes data in a non-diabetic population.

Commonly reported

• Nausea — most common dose-limiting side effect, typically dose-dependent and most pronounced during titration steps
• Vomiting
• Diarrhea
• Constipation
• Decreased appetite (often reported as a benefit; extreme cases warrant dose reduction)
• Fatigue
• Injection site reactions
• Anhedonia and mood flattening (reported across the incretin class)
• Headache
• Hypoglycemia (uncommon as monotherapy; more common when combined with insulin or sulfonylureas in T2D contexts)

Serious

• Severe persistent vomiting or signs of dehydration
• Acute pancreatitis symptoms (severe abdominal pain radiating to back)
• Gallbladder symptoms (right upper quadrant pain, jaundice) — gallstones and cholecystitis reported at elevated rates in semaglutide trials
• Acute kidney injury (typically secondary to dehydration from GI side effects)
• Diabetic retinopathy worsening (observed in T2D contexts, especially when adding semaglutide on top of existing diabetes therapy)
• Suicidal ideation or new-onset mood changes (under regulatory review across the incretin class as of 2024–2025)

Personal or family history of medullary thyroid carcinoma (MTC) or Multiple Endocrine Neoplasia syndrome type 2 (MEN2) — FDA-mandated boxed warning across the incretin class, based on rodent thyroid C-cell tumor findings; human relevance is debated but the warning is legally binding for prescribers in the US

History of pancreatitis

Severe gastrointestinal disease (gastroparesis especially — semaglutide further slows gastric emptying)

Severe renal impairment (limited data; dehydration risk amplifies)

Concurrent use of other GLP-1, GIP, or glucagon receptor agonists

Pregnancy and lactation: not recommended. Animal studies showed reproductive toxicity; the Wegovy and Ozempic labels recommend discontinuation at least 2 months before a planned pregnancy due to the long half-life

GLP-1 receptor agonist

A compound that switches on the GLP-1 receptor, the same target a natural gut hormone uses to signal fullness and help regulate blood sugar.

Subcutaneous

An injection into the fatty layer just under the skin, rather than into a muscle or vein.

Half-life

Roughly how long the body takes to clear half of a dose. A long half-life is why some compounds can be taken only once a week.

Titration

Starting at a low dose and increasing it gradually.

1. Wilding JPH, Batterham RL, Calanna S, Davies M, Van Gaal LF, Lingvay I, McGowan BM, Rosenstock J, Tran MTD, Wadden TA, Wharton S, Yokote K, Zeuthen N, Kushner RF, for the STEP 1 Study Group. (2021). Once-Weekly Semaglutide in Adults with Overweight or Obesity. New England Journal of Medicine, 384(11):989–1002.(PMID 33567185 · NCT03548935)
2. Lincoff AM, Brown-Frandsen K, Colhoun HM, Deanfield J, Emerson SS, Esbjerg S, Hardt-Lindberg S, Hovingh GK, Kahn SE, Kushner RF, Lingvay I, Oral TK, Michelsen MM, Plutzky J, Tornøe CW, Ryan DH, for the SELECT Trial Investigators. (2023). Semaglutide and Cardiovascular Outcomes in Obesity without Diabetes. New England Journal of Medicine, 389(24):2221–2232.(PMID 37952131 · NCT03574597)
3. Marso SP, Bain SC, Consoli A, et al., for the SUSTAIN-6 Investigators. (2016). Semaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes. New England Journal of Medicine, 375(19):1834–1844.(PMID 27633186 · NCT01720446)
4. Aroda VR, Rosenstock J, Terauchi Y, et al., for the PIONEER 1 Investigators. (2019). PIONEER 1: Randomized Clinical Trial of the Efficacy and Safety of Oral Semaglutide Monotherapy in Comparison With Placebo in Patients With Type 2 Diabetes. Diabetes Care, 42(9):1724–1732.(PMID 31186300 · NCT02906930)
5. Lau J, Bloch P, Schäffer L, Pettersson I, Spetzler J, Kofoed J, Madsen K, Knudsen LB, McGuire J, Steensgaard DB, Strauss HM, Gram DX, Knudsen SM, Nielsen FS, Thygesen P, Reedtz-Runge S, Kruse T. (2015). Discovery of the Once-Weekly Glucagon-Like Peptide-1 (GLP-1) Analogue Semaglutide. Journal of Medicinal Chemistry, 58(18):7370–7380.(PMID 26308095)
6. Novo Nordisk. Ozempic (semaglutide) injection prescribing information. US Food and Drug Administration. NDA 209637, label SUPPL-038 approved 2026-06-01 (Revised 05/2026).
7. McCrimmon RJ, Catarig AM, Frias JP, Lausvig NL, le Roux CW, Thielke D, Lingvay I. (2020). Effects of once-weekly semaglutide vs once-daily canagliflozin on body composition in type 2 diabetes: a substudy of the SUSTAIN 8 randomised controlled clinical trial. Diabetologia, 63(3):473–485.(PMID 31897524 · NCT03136484)
8. Novo Nordisk. Wegovy (semaglutide) injection prescribing information. US Food and Drug Administration. NDA 215256, label SUPPL-025 approved 2026-06-18 (Revised 06/2026; the same label also covers Wegovy tablets, NDA 218316).
9. Novo Nordisk. Wegovy® approved by FDA for the treatment of adults with noncirrhotic MASH with moderate to advanced liver fibrosis. Press release, August 15, 2025.
10. Novo Nordisk. FDA approves Ozempic® (semaglutide) as the only GLP-1 RA to reduce the risk of worsening kidney disease and cardiovascular death in adults with type 2 diabetes and chronic kidney disease. Press release, January 28, 2025.
11. Novo Nordisk. FDA approves Novo Nordisk's oral semaglutide for cardiovascular (CV) risk reduction in adults with type 2 diabetes who are at high risk, including those who have not had a prior CV event. Press release, October 17, 2025.(NCT03914326)
12. Bonaca MP, et al. (2025). Semaglutide and walking capacity in people with symptomatic peripheral artery disease and type 2 diabetes (STRIDE): a phase 3b, double-blind, randomised, placebo-controlled trial. The Lancet, 405(10489):1580–1593.(PMID 40169145)
13. Cummings JL, Atri A, Sano M, Zetterberg H, Scheltens P, Knop FK, Johannsen P, Wichmann CA, Abschneider RM, Leon T, Feldman HH. (2026). Efficacy and safety of oral semaglutide (flexible dose) in early-stage symptomatic Alzheimer's disease (evoke and evoke+): two phase 3, randomised, placebo-controlled trials. The Lancet, 407(10544):2167–2179.(PMID 41865758)
14. Novo Nordisk. Wegovy® approved in the US for cardiovascular risk reduction in people with overweight or obesity and established cardiovascular disease. Company announcement No 21/2024, 8 March 2024.
15. Novo Nordisk. FDA approves Novo Nordisk's Wegovy® pill, the first and only oral GLP-1 for weight loss in adults. Press release, December 22, 2025.
16. US Food and Drug Administration. NDA 213051/S-030 supplement approval letter (01/30/2026): accessdata.fda.gov/drugsatfda_docs/appletter/2026/213051Orig1s030ltr.pdf, to "change the name of the product from Rybelsus (formulation R2) to Ozempic (semaglutide) tablets", with the label approved with it (Revised 1/2026): accessdata.fda.gov/drugsatfda_docs/label/2026/213051Orig1s030lbl.pdf. And Novo Nordisk, Novo Nordisk's Ozempic® pill, the only FDA-approved oral peptide GLP-1 medication for adults with type 2 diabetes, soon to be available in the US, press release, May 1, 2026: prnewswire.com/news-releases/novo-nordisks-ozempic-pill-the-only-fda-approved-oral-peptide-glp-1-medication-for-adults-with-type-2-diabetes-soon-to-be-available-in-the-us-302760106.html. "starting Monday, May 4, Ozempic® (semaglutide) tablets, and will be available for adults with type 2 diabetes in the US"; "Rybelsus® will continue to be marketed outside the US." Source for: the US rename, the Ozempic tablets dosing schedule and the switching rule (label §2.2–2.3).

• CJC-1295 / Ipamorelin Blend — discussed together in this entry's stacks section
• BPC-157 / TB-500 Blend — discussed together in this entry's stacks section
• Tesamorelin — discussed together in this entry's stacks section
• Amycretin — same mechanism class
• CagriSema — same mechanism class
• Dulaglutide — same mechanism class