Semaglutide: 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 seven-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 14.9 percent at 68 weeks (Wilding et al., NEJM 2021). That trial is the reference point most later work is measured against, and it is the reason semaglutide became the baseline expectation for the class rather than an outlier result.

For scale, trials report 20.9 percent mean reduction at 72 weeks for tirzepatide, a dual agonist (Jastreboff et al., NEJM 2022), and 25.0 percent at 80 weeks for investigational retatrutide, a triple agonist, in a Phase 3 trial (Jastreboff et al., NEJM 2026). The comparison has real limits and they are worth stating plainly: these are separate trials, run in different populations, over different durations, with different designs and endpoints. Lining the percentages up in a row is a convenience, not a head-to-head result.

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.

Several regulatory changes followed in 2025 and 2026. An oral tablet was approved by the US FDA for chronic weight management in December 2025; a trial of the oral form reports a mean body-weight reduction of 13.6 percent at 64 weeks against 2.2 percent with placebo (Wharton et al., NEJM 2025). In August 2025 the FDA granted accelerated approval for MASH with moderate to advanced liver fibrosis, after a Phase 3 trial reported resolution of steatohepatitis without worsening of fibrosis in 62.9 percent of patients against 34.3 percent with placebo at 72 weeks (Sanyal et al., NEJM 2025). On safety, Australia's TGA added a rare risk of non-arteritic anterior ischaemic optic neuropathy, a cause of sudden vision loss, to GLP-1 product information in July 2026, with its expert committee finding that the evidence may support the signal for semaglutide (TGA, 2026). 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 the FDA proposed excluding semaglutide from the bulk substances that outsourcing facilities may compound from (FDA, 2026).

Sources (12)

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. Wilding et al., New England Journal of Medicine, 2021 — semaglutide (STEP 1 trial); the abstract reports a mean 14.9% body-weight reduction at week 68. PubMed 33567185
3. 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
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. Semaglutide — the US FDA label (section 12.3) states an elimination half-life of approximately 1 week. FDA label (DailyMed)
6. Wharton et al., New England Journal of Medicine, 2025 — oral semaglutide in adults with overweight or obesity; the abstract reports a mean 13.6% body-weight reduction at week 64 versus 2.2% with placebo. PubMed 40934115
7. Sanyal et al., New England Journal of Medicine, 2025 — Phase 3 trial of semaglutide in MASH; the abstract reports resolution of steatohepatitis without worsening of fibrosis in 62.9% versus 34.3% with placebo. PubMed 40305708
8. US FDA — approval of the oral tablet for chronic weight management, NDA 218316, December 2025. FDA approval letter
9. Semaglutide weight-management label — MASH indication under accelerated approval, and “about 5 to 7 weeks” in circulation after the last dose. FDA label (DailyMed)
10. TGA (Australia), Medicine Safety Update, 23 July 2026 — NAION warnings updated across the GLP-1 class. TGA safety update
11. 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
12. US FDA press announcement, 30 April 2026 — proposal to exclude semaglutide, tirzepatide and liraglutide from the 503B bulks list. FDA announcement

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

A half-life is the time taken for half of what is present to clear. At approximately seven days, weekly injections overlap heavily instead of clearing between them: levels build across the early weeks rather than returning to zero, which is why the cadence settles where it does.

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

Semaglutide differs from the investigational compounds in one important way: an approved product exists, and it has an official label. That label is where approved-product dosing lives, and 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 semaglutide 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 semaglutide record holds

Because the cadence is weekly, there are relatively few entries in a semaglutide 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; you can also see how Pepti compares to other trackers before you choose, or start with the peptide tracking app guide or our GLP-1 tracker for weekly injections. For the app side of logging it, see the semaglutide 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 semaglutide?

Semaglutide is a GLP-1 receptor agonist. It mimics an incretin hormone the gut releases after eating, acting on appetite signalling in the hypothalamus, slowing gastric emptying, and increasing glucose-dependent insulin secretion. It is given as a weekly subcutaneous injection or as a daily oral tablet.

Is semaglutide approved?

Yes. Semaglutide is approved in many jurisdictions for type 2 diabetes and for chronic weight management, and in the US for MASH with moderate to advanced liver fibrosis, which makes it unusual among the compounds people track: 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 semaglutide from the list of bulk substances that outsourcing facilities may compound from, finding no clinical need (FDA, 2026).

What is semaglutide's half-life?

Approximately seven days, about 168 hours. The FDA label (DailyMed) reports an elimination half-life of approximately one week. The half-life calculator on this site plots a decay curve from a half-life you enter. A half-life this long is the reason the cadence is weekly: successive injections overlap substantially rather than clearing between administrations, so levels build across the early weeks rather than returning to zero.

How is semaglutide different from tirzepatide and retatrutide?

They differ in how many receptors they act on. Semaglutide is a single agonist at the GLP-1 receptor. Tirzepatide is a dual agonist, adding GIP. Retatrutide is a triple agonist, adding glucagon, and is investigational rather than approved. Trials report larger mean body-weight reductions as the number of targets rises, but those figures come from separate trials with different populations, durations and designs, so they are not a head-to-head comparison.

Does compounded semaglutide need to be reconstituted?

It depends on the form in front of you. The approved product is supplied as a prefilled pen containing solution, already in liquid form and requiring 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 semaglutide 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.

How long does semaglutide stay in your system?

The FDA type 2 diabetes label (DailyMed) states that, with an elimination half-life of approximately one week, semaglutide will be present in the circulation for about five weeks after the last dose; the current weight-management label gives about five to seven weeks. Those are the labels' figures for the approved products.

When does semaglutide reach steady state?

The FDA label (DailyMed) states that steady-state exposure is achieved following four to five weeks of once-weekly administration. That fits the half-life of approximately one week: successive weekly injections overlap, so levels build across the early weeks before settling.

This page is a reference on published evidence and record-keeping. It does not recommend semaglutide 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.

Pepti, our iOS peptide tracker, keeps the weekly log, the site sequence, the vial records and the weight trend in one place.

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

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