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Semaglutide

Also known as: Ozempic, Rybelsus, Wegovy, NN9535, NNC 0113-0217

FDA Approved

Molecular Formula

C187 H291 N45 O59

Molecular Weight

4,113.58 Da

Half-Life

~168 hours (~7 days)

Sequence

H{Aib}EGTFTSDVSSYLEGQAAK((AEEA)2-γ-Glu-C18 diacid)EFIAWLVRGRG-OH (Aib-2 substitution; Lys-26 modified with C18 fatty diacid spacer)

Clinical Applications & Evidence

Mechanism of Action

Semaglutide selectively binds and activates the GLP-1 receptor, enhancing glucose-dependent insulin secretion, suppressing glucagon secretion, and activating hypothalamic and brainstem vagal satiety networks to reduce caloric intake. It produces a transient delay in gastric emptying that is most pronounced after initial administration. Albumin binding enabled by a C18 fatty diacid spacer at Lys-26 and DPP-4 resistance via Aib-2 substitution extend elimination half-life to approximately one week.

Investigated Uses

  • Type 2 Diabetes Mellitus (FDA-approved as Ozempic & Rybelsus; reduces MACE and CKD progression)
  • Chronic Weight Management (FDA-approved as Wegovy injection & tablets; reduces MACE in adults with CVD)
  • Noncirrhotic MASH with F2–F3 Fibrosis (FDA accelerated approval as Wegovy injection)
  • Alzheimer's Disease (Investigational — Phase 3 EVOKE & EVOKE+ trials failed to show statistically significant reduction in disease progression)
  • PCOS & Epigenetic Aging (Investigational — Exploratory weight management & post-hoc biomarker studies; not FDA-approved)
Extensive Clinical Data

Regulatory & Safety Status

FDA Status

FDA Approved

WADA / Athletic Status

Not Explicitly Prohibited

Known Side Effects

Boxed Warning: Thyroid C-cell tumor risk in rodent studies; human relevance unestablishedGastrointestinal events (nausea, vomiting, diarrhea, abdominal pain, constipation, dyspepsia)Acute pancreatitis, acute gallbladder disease, and acute kidney injury secondary to volume depletionDiabetic retinopathy complications in patients with type 2 diabetes and rapid glucose reductionHypoglycemia risk when coadministered with insulin secretagogues or exogenous insulinPeri-procedural pulmonary aspiration risk during general anesthesia or deep sedation

Contraindications

  • Personal or family history of medullary thyroid carcinoma (MTC) or MEN2 syndrome
  • Known serious hypersensitivity to semaglutide or product excipients
  • Pregnancy (Wegovy should be discontinued when pregnancy is recognized; Ozempic/Rybelsus require 2-month pre-conception washout)
  • Severe gastroparesis or severe active gastrointestinal disease (Precautionary exclusion)

Drug Interactions

  • Insulin secretagogues and exogenous insulin (Increased hypoglycemia risk; dose reduction may be required)
  • Oral semaglutide specific administration (Must be taken on an empty stomach with ≤4 oz water, 30 min before food, drink, or other oral medications)
  • Levothyroxine (Oral semaglutide increased levothyroxine exposure in clinical studies; thyroid monitoring recommended)

Citations & Clinical Trials

FDA Ozempic (semaglutide) Prescribing Information (FDA 2026) FDA Wegovy (semaglutide) Prescribing Information & MASH Approval (FDA 2026) GlobeNewswire / Novo Nordisk Novo Nordisk Phase 3 EVOKE Trials Topline Results in Alzheimer's Disease (2025) FDA FDA Announcement: Semaglutide Shortage Resolution & Compounding Status Nature Communications Epigenetic Aging Biomarker Analysis Following Semaglutide Treatment (Nat Commun 2026) USADA USADA Athlete Guidance on GLP-1 Agonists and WADA Status (2026)