Wegovy (Semaglutide) Half-Life
Wegovy (semaglutide 2.4 mg) has an elimination half-life of approximately 7 days (approximately 165 hours), which allows for once-weekly subcutaneous administration and means it reaches steady-state concentrations in 4–5 weeks. 1, 2
Pharmacokinetic Profile
The long half-life of semaglutide is achieved through three key structural modifications: attachment of a C18 fatty diacid side chain (lipidation), substitution of Aib8 for Ala8, and replacement of Lys26 with Arg26, which together promote strong albumin binding and protect against enzymatic degradation. 2
At therapeutic doses of 0.5 mg or 1.0 mg subcutaneously once weekly, semaglutide maintains a consistent half-life of approximately 7 days, supporting the once-weekly dosing regimen. 2
Steady-state plasma concentrations are achieved after 4–5 weeks of once-weekly dosing, reflecting the accumulation kinetics expected from the 7-day half-life. 1, 2
Clinical Implications of the Long Half-Life
The extended half-life provides stable, predictable pharmacokinetics with minimal peak-to-trough fluctuation, which contributes to sustained glycemic control and appetite suppression throughout the dosing interval. 1
If a dose is missed, semaglutide should be administered as soon as possible if ≤5 days have elapsed since the scheduled dose; if >5 days have passed, skip the missed dose and resume at the next scheduled weekly dose. 3 This guidance reflects the drug's long half-life, which maintains therapeutic levels for several days after a missed dose.
When discontinuing semaglutide, the drug will remain in the body for approximately 5 half-lives (roughly 35 days or 5 weeks) before being fully eliminated, which is clinically relevant for peri-operative planning and when switching to alternative therapies. 1, 2
Comparison: Oral vs. Subcutaneous Formulations
Oral semaglutide (Rybelsus) has the same elimination half-life of approximately 7 days once absorbed, but its bioavailability is only 0.8% under recommended dosing conditions (taken with ≤120 mL water, 30-minute post-dose fasting). 4
The within-subject variability in oral bioavailability is 137% for individual doses, but this translates to only 33% variability in steady-state exposure due to the long half-life and daily dosing, demonstrating how the extended half-life buffers against absorption variability. 4
Special Populations
No dose adjustment is required for renal impairment (including eGFR <30 mL/min/1.73 m²) or hepatic impairment, as the half-life and clearance remain unchanged across these populations. 3, 1
Body weight may influence semaglutide exposure (higher body weight associated with lower exposure), but the clinical significance is limited and dose adjustments based on weight are not recommended. 1
Peri-Operative Considerations
For elective surgery requiring anesthesia, semaglutide should be discontinued at least 3 weeks (approximately 3 half-lives) before the procedure to minimize delayed gastric emptying and aspiration risk, as retained gastric contents have been documented even after extended fasting periods. 3
The 7-day half-life means that gastric-emptying effects persist for 10–14 days after the last dose, which is why a 3-week discontinuation period is recommended rather than a shorter interval. 3