From the Guidelines
The half-life of semaglutide is approximately 7 days. This extended half-life is what allows semaglutide to be administered as a once-weekly injection for conditions like type 2 diabetes and obesity, rather than requiring daily dosing, as noted in a recent study published in Anaesthesia in 2025 1. The long half-life results from semaglutide's molecular structure, which includes a fatty acid side chain that binds to albumin in the bloodstream, protecting it from rapid degradation and renal clearance.
Some key properties of semaglutide include:
- Administration route: subcutaneous (SC) or oral
- Total dose range: 0.25 - 4.5 mg
- Bioavailability: 10.3 nmol.l
- Volume of distribution: 0.8% (oral), 89% (SC)
- Fraction bound to plasma protein: 8
- Major elimination route: metabolised
- Active metabolite: no
This pharmacokinetic profile provides consistent blood levels of the medication, which helps maintain glycemic control and appetite suppression effects throughout the weekly dosing interval, improving patient adherence compared to medications requiring more frequent administration, as seen with other GLP-1 receptor agonists like dulaglutide and liraglutide, which have shorter half-lives of 4.5 days and 13 hours, respectively 1.
From the FDA Drug Label
With an elimination half-life of approximately 1 week, semaglutide will be present in the circulation for about 5 weeks after the last dose. The half-life of semaglutide is approximately 1 week 2.
From the Research
Half-Life of Semaglutide
- The half-life of semaglutide is approximately 7 days, allowing for once-weekly subcutaneous administration 3.
- This half-life enables semaglutide to reach steady state in 4-5 weeks 3.
- A study on the conversion of semaglutide from once-weekly to once-monthly dosing reported an in vivo half-life of released semaglutide of approximately 36 days 4.
- A systematic review of the clinical pharmacokinetics of semaglutide confirmed its predictable pharmacokinetic profile with a long half-life, supporting once-weekly subcutaneous administration 5.
Factors Affecting Half-Life
- Food and various dosing conditions, including water volume and dosing schedules, can affect the oral semaglutide exposure, but the half-life remains relatively consistent 5.
- Body weight may affect semaglutide exposure, but further studies are needed to confirm this 5.
- There are limited drug-drug interactions and no dosing adjustments are necessary in patients with upper gastrointestinal disease, renal impairment, or hepatic impairment 3, 5.