Tirzepatide: evidence, half-life, and how to track it

By Tessaro Pty Ltd, the maker of Pepti · Last reviewed October 2026

This page is a reference, not a protocol. It sets out what the published trials actually report, what a five-day half-life means for a weekly record, and what a clean log holds. It contains no dose figures and no schedule, and the section further down explains why that is deliberate rather than an omission.

Reference

What trials report

Published data describe a mean body-weight reduction of 20.9 percent at 72 weeks (Jastreboff et al., NEJM 2022). That result is what moved the expectation for the class upward, and it is the figure most later comparisons are anchored to.

The more useful result came later, because it is the only head-to-head comparison of the two agents for weight management in people without diabetes. Aronne et al., NEJM 2025 report that tirzepatide produced greater mean body-weight reduction than semaglutide in a randomized comparison of the two agents, approximately 20.2 percent against 13.7 percent at 72 weeks. That distinction matters more than it may appear. The percentages our other pages line up side by side, including investigational retatrutide at 25.0 percent over 80 weeks in a Phase 3 trial (Jastreboff et al., NEJM 2026), come from separate trials with different populations, durations and designs, and carry an explicit caveat that they are not comparable. This one does not need that caveat: the two agents were compared in the same trial, in the same population, over the same period. Other randomized trials have also compared tirzepatide directly with another incretin medicine in type 2 diabetes, including one against semaglutide, reporting greater reductions in HbA1c and body weight with tirzepatide (Frías et al., NEJM 2021), and a cardiovascular outcomes trial against dulaglutide, in which tirzepatide was non-inferior for cardiovascular death, heart attack or stroke (Nicholls et al., NEJM 2025).

The figure that matters most to a record, though, is not an efficacy number at all. Published data describe one-year discontinuation of GLP-1 therapy of 64.8 percent among adults without type 2 diabetes (Rodriguez et al., JAMA Network Open 2025), meaning roughly two in three stop within a year. Whatever drives that in an individual case, it makes the dated history unusually valuable: when the conversation with whoever directs your use turns to whether to continue, a complete record of what was taken, when, and what was observed alongside it is the only evidence in the room that is actually about you.

The US label gained two new indications in the past year. In December 2025 it was extended to children aged 10 and over with type 2 diabetes, after a trial reported a greater reduction in HbA1c than placebo at 30 weeks (Hannon et al., Lancet 2025), and in August 2026 to reducing the risk of major cardiovascular events in adults with type 2 diabetes at high cardiovascular risk (FDA label, DailyMed). In January 2026 the US FDA asked for the suicidal-behaviour warning to be removed from weight-management GLP-1 labels after a meta-analysis of 91 placebo-controlled trials found no increased risk (FDA, 2026), and in April 2026 it proposed excluding tirzepatide from the bulk substances that outsourcing facilities may compound from (FDA, 2026). Australia's TGA updated optic-neuropathy (NAION) warnings across the GLP-1 class in July 2026, though its expert committee found the evidence may support the signal for semaglutide but not tirzepatide (TGA, 2026).

Sources (11)

1. Jastreboff et al., New England Journal of Medicine, 2026 — retatrutide Phase 3 trial in obesity without diabetes (TRIUMPH-1); the abstract reports a 25.0% body-weight reduction at week 80 in the highest-dose group versus 3.9% with placebo. PubMed 42814954
2. Jastreboff et al., New England Journal of Medicine, 2022 — tirzepatide (SURMOUNT-1); the abstract reports a 20.9% body-weight reduction at week 72 (highest-dose group). PubMed 35658024
3. Aronne et al., New England Journal of Medicine, 2025 — head-to-head comparison (SURMOUNT-5); the abstract reports tirzepatide 20.2% vs semaglutide 13.7% body-weight reduction at week 72. PubMed 40353578
4. Rodriguez et al., JAMA Network Open, 2025 — GLP-1 discontinuation and reinitiation; the abstract reports 64.8% one-year discontinuation in adults without type 2 diabetes. PubMed 39888616
5. Tirzepatide — the US FDA label (section 12.3) states an elimination half-life of approximately 5 days; the same label lists the paediatric type 2 diabetes (12/2025) and cardiovascular-risk (08/2026) indications. FDA label (DailyMed)
6. Frías et al., New England Journal of Medicine, 2021 — tirzepatide versus semaglutide in type 2 diabetes (SURPASS-2); the abstract reports tirzepatide noninferior and superior on HbA1c, with greater body-weight reductions. PubMed 34170647
7. Nicholls et al., New England Journal of Medicine, 2025 — cardiovascular outcomes with tirzepatide versus dulaglutide (SURPASS-CVOT); the abstract reports a hazard ratio of 0.92 for the primary composite, noninferior. PubMed 41406444
8. Hannon et al., Lancet, 2025 — tirzepatide in children and adolescents with type 2 diabetes (SURPASS-PEDS); the abstract reports a greater HbA1c reduction than placebo at week 30. PubMed 40975112
9. US FDA Drug Safety Communication, 13 January 2026 — removal of the suicidal behaviour and ideation warning from weight-management GLP-1 labels. FDA Drug Safety Communication
10. US FDA press announcement, 30 April 2026 — proposal to exclude semaglutide, tirzepatide and liraglutide from the 503B bulks list. FDA announcement
11. TGA (Australia), Medicine Safety Update, 23 July 2026 — NAION warnings updated across the GLP-1 class. TGA safety update

What a five-day half-life means for your record

A half-life is the time taken for half of what is present to clear. At approximately five days, weekly injections still overlap rather than clearing between them, so levels build across the early weeks instead of returning to zero. The overlap is smaller than it is for a seven-day compound, which makes the timing of each injection somewhat more visible in how the week feels.

Two things follow for record-keeping. A missed week is a much larger gap than a missed day would be on a daily compound, so the log needs to make an absent week obvious at a glance rather than burying it. And because the curve is slow, what you notice in any given week is a product of several preceding weeks, not just the most recent injection, which makes the dated history far more informative than any single entry in it.

Why this page has no dosing section

Tirzepatide is an approved product with an official label, and that label is where approved-product dosing lives. It is a matter between you and whoever directs your use. Restating label figures on a tracking site adds nothing and risks a good deal, because a number copied out of context loses the conditions attached to it.

Compounded tirzepatide is a different situation again. Concentration varies from preparation to preparation, so a figure that was correct for one vial can be wrong for the next one, and no page can tell you what is in the vial in front of you. That is precisely why Pepti records the figures you already have rather than suggesting any of its own. The record is ours; the figure is not, and it never will be.

What a clean tirzepatide record holds

Because the cadence is weekly, there are relatively few entries in a tirzepatide log, which makes each one carry more weight. A record worth keeping holds the following.

The free reconstitution calculator on this site converts the figures you already have into a draw volume and a count of doses per vial, the injection site rotation guide sets out the zone system, and how to track peptide cycles covers the record-keeping method in full. See the peptide tracking app guide for what a tracker keeps in one place, or our GLP-1 tracker for weekly injections. For the app side of logging it, see the tirzepatide tracker app page. If hair shedding is something you are logging, see hair shedding on GLP-1s: what the evidence says.

Common questions

What is tirzepatide?

Tirzepatide is a dual agonist: it acts at both the GIP and the GLP-1 receptor, where earlier agents in the class act at GLP-1 alone. The practical consequence is effects on appetite signalling, gastric emptying and glucose-dependent insulin secretion through two incretin pathways rather than one. It is given as a weekly subcutaneous injection.

Is tirzepatide approved?

Yes. Tirzepatide is approved in multiple jurisdictions for type 2 diabetes and for chronic weight management, and in the US also for type 2 diabetes in children aged 10 and over and to reduce the risk of major cardiovascular events in adults with type 2 diabetes at high cardiovascular risk. That means an official label exists and the dosing in it is a matter for whoever directs your use. It is also widely used in compounded form, which is not the approved product and is not covered by that label. In April 2026 the US FDA proposed excluding tirzepatide from the list of bulk substances that outsourcing facilities may compound from, finding no clinical need (FDA, 2026).

What is tirzepatide's half-life?

Approximately five days, about 120 hours. The FDA label (DailyMed) reports an elimination half-life of approximately five days. The half-life calculator on this site plots a decay curve from a half-life you enter. A half-life of this length is why the cadence is weekly: successive injections overlap rather than clearing between administrations, so levels build across the early weeks instead of returning to zero each time.

Is tirzepatide more effective than semaglutide?

For weight loss in people without diabetes, the one direct randomized comparison published to date says yes. Aronne et al., NEJM 2025 report tirzepatide produced greater mean body-weight reduction than semaglutide, approximately 20.2 percent against 13.7 percent at 72 weeks. Two caveats matter. That is a mean across one trial population, and individual response varies widely, so a group average does not predict any one person's result. Effectiveness is also only one input into a decision that belongs to you and whoever directs your use.

Does compounded tirzepatide need to be reconstituted?

It depends on the form in front of you. The approved product is supplied ready to use as a solution and requires no mixing. Compounded material is commonly supplied as a lyophilized powder, which is inert until a diluent is added, and its concentration varies between preparations rather than being fixed. These are different physical products, and a record that does not say which one it describes is ambiguous later.

Does Pepti tell me what dose to take?

No. Pepti supplies no dose figures for tirzepatide or for anything else. It records the figure you already have from whoever directs your use, with the date, time, injection site and vial, and keeps the 12-zone site sequence. The record is ours; the figure is not.

When does tirzepatide reach steady state?

The FDA label (DailyMed) states that steady-state plasma tirzepatide concentrations were achieved following four weeks of once-weekly administration. With a half-life of approximately five days, successive weekly injections overlap, so levels build across the early weeks before settling.

How long does it take tirzepatide to get out of your system?

The US label gives an elimination half-life of approximately 5 days and does not state a clearance date. Arithmetic on that figure: about half remains after 5 days, about 3 percent after five half-lives, roughly 25 days, and under 1 percent after seven. Where levels sit in any one person is a question for whoever directs your use; this page supplies the label figure and the arithmetic only.

Which GLP-1 has the shortest half-life?

Of the two approved weekly compounds covered on this site, tirzepatide: its US label gives an elimination half-life of approximately 5 days, against approximately 1 week for semaglutide on its label. Both figures come from the labels, and both are long enough for the once-weekly cadence the labels describe.

This page is a reference on published evidence and record-keeping. It does not recommend tirzepatide or any other substance, and it provides no dose figure, no titration amount, and no schedule. Approved-product dosing is a matter for the official label and for whoever directs your use.

Track it in Pepti — the weekly log, the site sequence, the vial records and the weight trend, kept in one place.

Not medical advice. Pepti is a record-keeping tool, not a medical device.

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