What semaglutide is
Semaglutide is a structural analog of the native incretin hormone glucagon-like peptide-1 (GLP-1), modified to resist rapid enzymatic degradation and to bind reversibly to serum albumin. Two specific modifications give semaglutide its pharmacological profile:[1][4]
- Position 26 (Lys) carries a hydrophilic spacer (γ-Glu–2×OEG) linked to a C18 fatty acid. This fatty-acid tail binds reversibly to albumin, markedly slowing renal clearance.
- Position 8 (Aib substitution) protects the peptide backbone from cleavage by dipeptidyl peptidase-4 (DPP-4), the enzyme that degrades native GLP-1 within minutes.
These two modifications are the reason semaglutide has a half-life measured in days rather than minutes.
Mechanism
Semaglutide selectively binds and activates the GLP-1 receptor. Downstream effects that underlie its glucose-lowering and weight-loss activity include:[2]
- Glucose-dependent insulin secretion from pancreatic β-cells (the incretin effect). Because stimulation is glucose-dependent, semaglutide rarely causes hypoglycemia on its own.
- Suppression of glucagon secretion from pancreatic α-cells, also glucose-dependent.
- Delayed gastric emptying, contributing to lower post-prandial glucose excursions and greater satiety.
- Central appetite modulation through GLP-1 receptors in hypothalamic and brainstem regions involved in food intake and reward.
Pharmacokinetics
Key parameters are summarized in the FDA prescribing information and reviewed in the peer-reviewed literature:[1][2][3]
- Absolute subcutaneous bioavailability: approximately 89%.
- Elimination half-life: approximately 1 week (roughly 165 hours), consistent across subcutaneous and oral formulations.
- Time to maximum plasma concentration (Tmax): 1 to 3 days after a subcutaneous dose.
- Steady state: reached after approximately 4 to 5 weeks of once-weekly dosing; this is why titration schedules in the FDA label step up the dose at 4-week intervals.
- Metabolism: proteolytic cleavage of the peptide backbone and sequential β-oxidation of the fatty-acid sidechain.
- Excretion: via both urine and feces; renal impairment does not require dose adjustment in the approved labels.
Storage and handling
- Ozempic / Wegovy pens. Store refrigerated at 2–8 °C before first use. After first use, the pen may be kept refrigerated or at room temperature up to 30 °C for up to the period specified on the FDA label for your product. Do not freeze; discard if frozen.
- Compounded vials. Handling depends on the preparing pharmacy's instructions. Compounded semaglutide commonly uses bacteriostatic water (0.9% benzyl alcohol) or sterile water. Reconstituted peptide drug products are typically stored refrigerated at 2–8 °C; specific beyond-use dates are set by the pharmacy.
- General. Avoid vigorous shaking and freeze–thaw cycles. Discard solutions that are cloudy, discolored, or contain particulates.
Reconstitution math (compounded vials)
Ozempic and Wegovy pens deliver pre-measured doses labeled directly in milligrams — users of those products do not perform unit math. The math below applies to compounded semaglutide dispensed as a lyophilized powder in a vial, which must be reconstituted before first use. Math does not recommend a dose.
Example 1 · 5 mg vial + 2 mL bac water
concentration = 5 mg / 2 mL = 2.5 mg/mL = 2500 mcg/mL
1 unit = 0.01 mL = 25 mcg
→ 0.25 mg (250 mcg) = 10 units
→ 0.5 mg (500 mcg) = 20 units
→ 1 mg (1000 mcg) = 40 units
→ 1.7 mg (1700 mcg) = 68 units
→ 2.4 mg (2400 mcg) = 96 units
Example 2 · 10 mg vial + 2 mL bac water
concentration = 10 mg / 2 mL = 5 mg/mL = 5000 mcg/mL
1 unit = 0.01 mL = 50 mcg
→ 0.25 mg = 5 units
→ 0.5 mg = 10 units
→ 1 mg = 20 units
→ 2 mg = 40 units
→ 2.4 mg = 48 units
Example 3 · 5 mg vial + 5 mL bac water
concentration = 5 mg / 5 mL = 1 mg/mL = 1000 mcg/mL
1 unit = 0.01 mL = 10 mcg
→ 0.25 mg = 25 units
→ 0.5 mg = 50 units
→ 1 mg = 100 units (full syringe)
Doses on the Ozempic titration schedule (0.25 mg, 0.5 mg, 1 mg, 2 mg) and the Wegovy titration schedule (0.25 mg → 0.5 mg → 1 mg → 1.7 mg → 2.4 mg) are drawn from the same math when working with a compounded vial — only the concentration you chose at reconstitution changes the unit count.
Frequently asked questions
What is the half-life of semaglutide?
About one week (roughly 165 hours). Steady state is reached in 4–5 weeks of once-weekly dosing.[1][3]
How is the long half-life achieved?
A C18 fatty acid at position 26 binds reversibly to serum albumin, slowing clearance; a position-8 modification protects against DPP-4 cleavage.[4]
How do I reconstitute a compounded semaglutide vial?
Typical: 5 mg vial + 2 mL bacteriostatic water = 2.5 mg/mL → 1 unit = 25 mcg, 250 mcg = 10 units, 1 mg = 40 units. Commercial pens are pre-filled and are not user-reconstituted.
How many units equal 0.25 mg?
At 2.5 mg/mL (5 mg in 2 mL), 0.25 mg = 10 units. At 5 mg/mL (10 mg in 2 mL), 0.25 mg = 5 units. At 1 mg/mL (5 mg in 5 mL), 0.25 mg = 25 units.
Is semaglutide FDA-approved?
Yes — as Ozempic, Wegovy, and Rybelsus. Compounded semaglutide sold outside those approved products is not itself FDA-approved.[1][2]
How long does it stay in your system after stopping?
Typically 5–6 weeks to clear to negligible plasma concentrations (5–7 half-lives). Appetite effects taper across that window; individual experience varies.
Primary references
- U.S. Food and Drug Administration. OZEMPIC (semaglutide) injection — full prescribing information. Updated label, 2023. accessdata.fda.gov — Ozempic label
- U.S. Food and Drug Administration. WEGOVY (semaglutide) injection — full prescribing information. Updated label, 2023. accessdata.fda.gov — Wegovy label
- Hall S, Isaacs D, Clements JN. Pharmacokinetics and clinical implications of semaglutide: a new glucagon-like peptide (GLP)-1 receptor agonist. Clin Pharmacokinet, 2018 (PubMed 29915923). PubMed
- Lau J, Bloch P, Schäffer L, et al. Discovery of the once-weekly glucagon-like peptide-1 (GLP-1) analogue semaglutide. J Med Chem, 2015. (Structure and albumin-binding modification.)
- Ahmann AJ, et al. Semaglutide — StatPearls. NCBI Bookshelf (NBK603723). ncbi.nlm.nih.gov — StatPearls