For healthcare professionals
Rybelsus for healthcare professionals
Clinical reference for Rybelsus (semaglutide (oral)) — mechanism of action, pharmacokinetics, indications, contraindications, key drug interactions, NDC codes, and FDA approval history.
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Mechanism of action
Pharmacology class
GLP-1 receptor agonist (oral)
Oral semaglutide is co-formulated with the absorption enhancer SNAC (sodium N-(8-(2-hydroxybenzoyl)amino)caprylate), which transiently raises localized gastric pH and protects the peptide from proteolytic degradation, enabling oral bioavailability of an otherwise injection-only molecule.
Pharmacokinetics
- Half-life
- ~7 days (equivalent to injectable semaglutide)
- T-max
- ~1 hour
- Metabolism
- Proteolytic cleavage and fatty-acid beta-oxidation
- Excretion
- Renal and fecal
- Bioavailability
- ~1% (strict empty-stomach protocol required)
Contraindications
- Personal or family history of medullary thyroid carcinoma
- Multiple Endocrine Neoplasia syndrome type 2
- Known hypersensitivity to semaglutide
Key drug interactions
Not exhaustive. See the FDA label for the full interaction list.
| Interacting drug | Severity | Note |
|---|---|---|
| Levothyroxine | major | Increased levothyroxine exposure — monitor thyroid function. |
| Insulin | major | Hypoglycemia risk. |
| Sulfonylureas | major | Hypoglycemia risk. |
| Oral medications (general) | moderate | Empty-stomach dosing window affects co-administered oral drug absorption. |
NDC codes & AWP
Representative NDC codes
- 0169-4304-30 (3 mg)
- 0169-4307-30 (7 mg)
- 0169-4314-30 (14 mg)
AWP per month (US, 2026 estimate)
~$1,029 AWP
FDA approval history
2019
Initial FDA approval — first oral GLP-1 receptor agonist for type 2 diabetes.
2023
Supplemental approval for cardiovascular event risk reduction in T2D + CV disease.
References
Sourcing Rybelsus for your patients
Compare US telehealth and pharmacy partners that dispense Rybelsus — useful when a patient asks about cash-pay options outside of their insurance formulary.
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