What is the duration of action of Ozempic (semaglutide) in the body?

Duration of Action of Ozempic (Semaglutide) in the Body

Semaglutide (Ozempic) has a long half-life of approximately 1 week, which means it remains active in your body for about 5 weeks after the last dose.

Pharmacokinetic Properties

Semaglutide has unique pharmacokinetic properties that contribute to its extended duration in the body:

• Half-life: Approximately 7 days 1
• Steady state: Reached after 4-5 weeks of regular dosing 1
• Elimination time: It takes about 5 half-lives (approximately 5 weeks) for the drug to be completely eliminated from the body 2

Mechanism for Extended Duration

The prolonged action of semaglutide is primarily due to:

1. Albumin binding: The main protraction mechanism is binding to albumin, facilitated by modification of position 26 lysine with a hydrophilic spacer and a C18 fatty di-acid 2
2. Metabolic stability: Semaglutide is modified in position 8 to provide stabilization against degradation by the enzyme dipeptidyl-peptidase 4 (DPP-4) 2
3. Reduced renal clearance: The albumin binding results in decreased renal clearance 2

Clinical Implications of Extended Duration

The long duration of action has several important clinical implications:

For Patients with Diabetes or Obesity

• Weekly dosing: The long half-life allows for once-weekly administration rather than daily dosing 1
• Steady blood levels: Provides consistent glycemic control throughout the week 2
• Washout period: For women planning pregnancy, semaglutide should be discontinued at least 2 months before conception due to the long washout period 2

For Perioperative Considerations

• Prolonged gastric effects: Semaglutide delays gastric emptying, which can persist for weeks after discontinuation 3
• Increased aspiration risk: Several case reports document regurgitation and pulmonary aspiration in patients undergoing surgery despite prolonged fasting periods (up to 20 hours) and even when semaglutide was stopped 4-6 days before surgery 3

Overdose Management

In the event of overdose, the FDA label notes:

• Appropriate supportive treatment should be initiated according to clinical signs and symptoms
• A prolonged period of observation and treatment may be necessary due to the long half-life of approximately 1 week 2

Future Developments

Research is underway to develop even longer-acting formulations:

• A microsphere-semaglutide formulation with a release half-life of approximately 36 days could potentially allow for once-monthly administration 4

Bottom Line

The extended duration of action of semaglutide (approximately 5 weeks after the last dose) is both its therapeutic advantage (allowing weekly dosing) and a consideration for certain clinical scenarios (pregnancy planning, perioperative management, and medication switching).