What is the pharmacokinetics of degradation of Ozempic (semaglutide)?

From the Guidelines

Ozempic (semaglutide) is primarily degraded through proteolysis and eliminated via urine and feces, with a half-life of approximately 1 week, allowing for once-weekly dosing. Specifically:

• Ozempic is metabolized by proteolytic cleavage of the peptide backbone and sequential beta-oxidation of the fatty acid side chain.
• The primary route of elimination is via urine and feces, with about 53% excreted in urine and 41% in feces.
• No intact semaglutide is excreted in urine or feces. The long half-life is due to:

1. Binding to albumin, which slows its elimination from circulation
2. Resistance to degradation by DPP-4 enzyme
3. Slow absorption from the subcutaneous injection site This pharmacokinetic profile allows for consistent blood levels with once-weekly injections, improving patient adherence compared to daily GLP-1 receptor agonists. The slow degradation and elimination also contribute to its prolonged glucose-lowering and weight loss effects, as supported by studies such as the SUSTAIN-6 trial 1 and the PIONEER 6 trial 1.

Key points to consider:

• The half-life of Ozempic allows for once-weekly dosing, which can improve patient adherence.
• The pharmacokinetic profile of Ozempic contributes to its prolonged glucose-lowering and weight loss effects.
• The elimination of Ozempic via urine and feces suggests that dose adjustments may be necessary in patients with renal or hepatic impairment, although specific guidance on this is not provided in the available evidence 1.

Overall, the pharmacokinetics of Ozempic support its use as a once-weekly GLP-1 receptor agonist for the treatment of type 2 diabetes, with a favorable profile for improving patient adherence and achieving prolonged glucose-lowering and weight loss effects.

From the FDA Drug Label

Metabolism The primary route of elimination for semaglutide is metabolism following proteolytic cleavage of the peptide backbone and sequential beta-oxidation of the fatty acid sidechain Elimination The apparent clearance of semaglutide in patients with type 2 diabetes is approximately 0. 05 L/h. 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 pharmacokinetics of degradation of Ozempic (semaglutide) involves metabolism as the primary route of elimination, with a half-life of approximately 1 week and an apparent clearance of 0.05 L/h. Semaglutide is degraded through proteolytic cleavage of the peptide backbone and sequential beta-oxidation of the fatty acid sidechain 2.

From the Research

Pharmacokinetics of Semaglutide

The pharmacokinetics of semaglutide, the active ingredient in Ozempic, has been studied in several clinical trials.

• The half-life of semaglutide is approximately 7 days, allowing for once-weekly subcutaneous administration 3.
• The area under the curve (AUC) and maximal plasma concentration (Cmax) of semaglutide increase with dose 4, 5.
• Food and dosing conditions can affect the exposure of oral semaglutide, but not subcutaneous semaglutide 4.
• There are limited drug-drug interactions, and no dosing adjustments are necessary for patients with renal or hepatic impairment 4, 3.

Degradation of Semaglutide

The degradation of semaglutide is not explicitly stated in the provided studies, but its pharmacokinetic profile suggests a predictable and stable degradation pattern.

• Semaglutide reaches steady state in 4-5 weeks, with a total exposure that increases in a dose-proportional manner 3, 5.
• The pharmacokinetics of semaglutide is consistent across different populations, including healthy Chinese subjects 5.

Clinical Implications

The pharmacokinetics of semaglutide has important implications for its clinical use.

• Semaglutide has been shown to be effective in reducing HbA1c levels and promoting weight loss in patients with type 2 diabetes 3, 6, 7.
• The incidence of gastrointestinal adverse effects increases with semaglutide dose 6.
• Semaglutide is generally well-tolerated, with a safety profile consistent with other GLP-1 receptor agonists 5, 7.