How long does Ozempic (semaglutide) stay in the system of a typical adult patient with normal renal and liver function?

How Long Ozempic Stays in Your System

Ozempic (semaglutide) has an elimination half-life of approximately 7 days (1 week), meaning it remains in your circulation for about 5 weeks after the last dose. 1

Pharmacokinetic Timeline

Half-Life and Elimination

• Semaglutide has a half-life of approximately 7 days, which is what allows for once-weekly dosing 1, 2
• The drug will be present in the circulation for approximately 5 weeks (about 35 days) after your last dose 1
• This extended presence is due to the drug's extensive binding to plasma albumin (>99%) and slow clearance rate 1

Time to Steady State

• Steady-state exposure is achieved after 4-5 weeks of once-weekly administration 1, 2
• This means it takes about a month of regular weekly injections for the drug to reach consistent levels in your system 1

Absorption and Peak Concentration

• Maximum concentration is reached 1-3 days after each injection 1
• The absolute bioavailability is 89% when administered subcutaneously 1

Metabolism and Excretion

How the Body Processes Semaglutide

• The primary elimination route is through metabolism via proteolytic cleavage of the peptide backbone and beta-oxidation of the fatty acid side chain 1
• The apparent clearance in patients with type 2 diabetes is approximately 0.05 L/h, which is quite slow 1

Excretion Pathways

• Only approximately 3% of the dose is excreted in urine as intact semaglutide 1
• The remainder is excreted as metabolites via both urine and feces 1

Clinical Implications of Extended Duration

Weight Regain After Stopping

• Significant weight regain occurs after discontinuation, with patients regaining 11.6% of lost weight over 52 weeks after stopping treatment 3
• In one trial, patients who transitioned to placebo after 20 weeks of treatment regained 6.9% of lost weight during 48 weeks of placebo administration 3
• This underscores that semaglutide requires long-term, potentially lifelong use to maintain weight loss benefits 3

Factors That Don't Affect Duration

• Age, sex, race, ethnicity, and renal impairment do not have clinically meaningful effects on semaglutide pharmacokinetics 1
• Hepatic impairment does not impact semaglutide exposure 1
• Body weight affects exposure (higher weight = lower exposure), but the standard doses provide adequate coverage across the weight range of 40-198 kg 1

Important Caveats

Drug Interactions

• The delay in gastric emptying caused by semaglutide may influence absorption of oral medications, though clinical studies showed no clinically relevant interactions with commonly co-administered drugs (metformin, oral contraceptives, warfarin, digoxin, atorvastatin) 1
• Semaglutide has very low potential to inhibit or induce CYP enzymes or drug transporters 1

Missed Doses

• If you miss 2 consecutive doses, you can resume at the same dose if previously well-tolerated 4
• If you miss 3 or more consecutive doses, consider restarting the full titration schedule 4

The 5-week presence in your system after stopping means that both therapeutic effects and potential side effects may persist for over a month after your last injection, which is crucial for planning any medication changes or surgical procedures.