How long GLP-1 medications stay in your system

What a half-life does and does not tell you

A half-life is the time it takes for the amount of a medicine in the blood to fall by half. One half-life leaves about 50%, two leave about 25%, three about 12.5%, and so on; nothing is gone after a single half-life. After five half-lives a little over 3% is left, which is why a medicine with a one-week half-life is still measurable weeks after the last dose.

The labels quote the elimination half-life measured in clinical pharmacology studies. It is an average for a population, not a reading of your own blood level. The PepLabo half-life calculator on this site illustrates the halving over time; it does not measure anything in your body.

The figures, molecule by molecule

The table restates the pharmacokinetic figures from section 12.3 of each US label, with European or Canadian numbers where they add something. Peak time is when the blood level is highest after a dose.

Why semaglutide and tirzepatide last so long

Natural GLP-1 lasts only 1.5 to 2 minutes in the blood, because enzymes break it down almost at once ^[7]. The long-acting medicines are built to resist that. Semaglutide carries a fatty acid chain that binds more than 99% of it to albumin, a blood protein; the labels say this lowers clearance by the kidneys and protects it from breakdown, and only about 3% of a dose leaves in the urine unchanged ^[1][2]. Tirzepatide uses a similar chain, is about 99% albumin-bound, and no intact tirzepatide is found in urine or feces ^[5].

Liraglutide is a once-daily design: the Saxenda® label attributes its 13-hour half-life to molecules clustering at the injection site, binding to plasma protein and resisting enzymes ^[7]. Orforglipron is a small molecule rather than a peptide. It is broken down mainly by the liver enzyme CYP3A4, and 87% of a dose was recovered in feces, less than 1% in urine ^[9].

Building up, as well as wearing off

The same half-life explains why levels rise over the first weeks. Each new dose adds to what remains of the earlier ones until intake and removal balance out, which is called steady state. For the weekly medicines that takes about a month, and for daily orforglipron about a week ^[1][5][6][9].

Blood level and effect do not always move together. The tirzepatide and orforglipron labels say the slowing of stomach emptying is greatest after the first dose and lessens over time, even while blood levels are still climbing towards steady state ^[5][9]. A level that is still present after the last dose therefore does not tell you how strongly you will feel the medicine.

What changes the figures, and what does not

• Kidneys: the Wegovy® label found no clinically significant change in semaglutide levels with reduced kidney function down to an eGFR of 30, and the Zepbound® and Trulicity® labels say kidney impairment does not affect tirzepatide or dulaglutide to a relevant degree ^[2][5][6].
• Liver: semaglutide levels did not differ meaningfully across mild to severe liver impairment, and tirzepatide was unchanged. Orforglipron is the exception: exposure rose 1.7-fold with moderate and 4.6-fold with severe liver impairment ^[2][5][9].
• Other medicines: strong CYP3A4 inhibitors raise orforglipron levels, so the Foundayo™ label caps the dose at 9 mg with them; strong inducers are to be avoided ^[9].
• Body weight, age and sex: the semaglutide and tirzepatide labels report no clinically relevant effect on their pharmacokinetics over the ranges studied ^[2][5].
• Speeding it up: no label describes a way to clear a GLP-1 medicine faster. After an overdose, the labels describe supportive treatment and, for semaglutide and tirzepatide, observation that may need to last longer because of the half-life ^[1][5].

Where the labels use these numbers

• Planning a pregnancy: the Ozempic®, Rybelsus® and Wegovy® labels ask women to leave at least 2 months between the last semaglutide dose and a planned pregnancy, given its long washout ^[1][2][3]. For tirzepatide, the EU Mounjaro® document and the Canadian Zepbound® monograph give at least 1 month, and the Canadian Trulicity® monograph gives the same for dulaglutide ^[11][13][14]. The US Zepbound® and Foundayo™ labels say to stop when pregnancy is recognised ^[5][9].
• Switching form: the Wegovy® label starts the 25 mg tablet one week after the last 2.4 mg injection, and the injection the day after the last tablet; the Rybelsus® label starts tablets one week after the last 0.5 mg Ozempic® injection ^[2][3].
• Overdose: observation and treatment may need to be prolonged, allowing for the half-lives: roughly a week for semaglutide, roughly 5 days for tirzepatide; the Foundayo™ label also points to its half-life ^[1][5][9].
• Procedures: the labels ask you to tell your healthcare providers about any planned surgery or procedure. The Ozempic® label says the available data are insufficient to say whether pausing the medicine reduces the risk of food remaining in the stomach ^[1].

Why the date of your last dose matters

Whether you are stopping, switching, planning a pregnancy or preparing for a procedure, the first thing a clinician will want to know is when your last dose was and how much it was. "About two weeks ago" is less useful than an exact date and strength, because every figure above is counted from that moment. Weight regain and blood sugar after stopping are covered in the article on stopping a GLP-1.

Ozempic®, Wegovy®, Rybelsus®, Saxenda® and Victoza® are registered trademarks of Novo Nordisk A/S. Mounjaro®, Zepbound® and Trulicity® are registered trademarks and Foundayo™ is a trademark of Eli Lilly and Company. PepLabo is not affiliated with or endorsed by Novo Nordisk or Eli Lilly and Company.

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