Semaglutide — the active ingredient in Ozempic, Wegovy, and Rybelsus — has a terminal half-life of approximately 168 hours, or about 7 days. A single weekly dose still has measurable plasma concentration roughly 5 weeks after the last injection. The slow clearance is by design: it's why the drug is dosed once weekly, why side effects fade gradually after stopping, and why a missed dose is usually buffered by residual drug from prior weeks. This article walks through the numbers from the FDA Ozempic label.
Semaglutide's terminal elimination half-life is approximately 168 hours (7 days), per the FDA Ozempic label. This is unusually long for a peptide drug — native GLP-1 has a half-life of about 2 minutes. Semaglutide achieves its weekly dosing by binding tightly to albumin, which protects it from renal filtration and DPP-4 degradation.
Why so long? A C18 fatty-diacid side chain anchors semaglutide to albumin; two amino-acid substitutions prevent DPP-4 cleavage; an AEEA linker preserves receptor potency. The net effect is a peptide that behaves like a small lipophilic molecule, with apparent clearance of ~0.05 L/h and volume ~12.5 L. Compare liraglutide (Saxenda, Victoza) — a shorter-linker GLP-1 that clears at ~1.2 L/h with a 13-hour half-life, requiring daily injection per the FDA Victoza/Saxenda label.
The standard pharmacokinetic rule is that a drug is "cleared" after 5 half-lives, when plasma drops below ~3% of peak. For semaglutide that's ~35 days, roughly 5 weeks, after the last dose. Trace amounts persist longer via albumin recycling, but they're clinically negligible.
Here is the math. Plasma concentration after a single dose follows C(t) = C₀ · 0.5^(t/t½). Plug in t½ = 168 h:
| Half-lives elapsed | Days since dose | % of peak remaining |
|---|---|---|
| 0 | 0 (at Tmax, ~day 2) | 100% |
| 1 | ~9 | 50% |
| 2 | ~16 | 25% |
| 3 | ~23 | 12.5% |
| 4 | ~30 | 6.25% |
| 5 | ~37 | 3.1% |
That 5-week tail is why StatPearls (Shaefer et al., 2024) recommends planning extra clearance time before any procedure where delayed gastric emptying could matter (anesthesia being the most-discussed example). It's also why people rarely see an immediate appetite "bounce" after stopping — the molecule is still circulating.
Subcutaneous semaglutide reaches peak plasma concentration (Tmax) at approximately 48 hours after injection. This is unusually slow — most SC peptides peak within 4–12 hours. The lag is driven by an absorption rate constant (kₐ) of just 0.015 h⁻¹, meaning the SC depot releases drug gradually over days.
This Tmax has practical implications. Side effects (nausea, GI discomfort) track plasma with a slight delay, so the worst day after an injection is often day 2 or day 3 — not the shot day itself. SC bioavailability is 89% per the FDA Ozempic label, so the depot eventually delivers nearly the full dose into circulation. The steady-state exposure in the SUSTAIN-6 cardiovascular outcomes trial fell within the range derivable from these PK parameters (Marso et al., NEJM 2016).
Between two weekly injections, plasma semaglutide rises to a peak around 48 hours post-dose, then falls along a 7-day half-life curve. Because the dosing interval (7 days) equals the half-life, plasma levels at the end of the week have dropped by roughly half — but the next dose lifts you back up before that ever bottoms out. Trough levels at steady state are ~50% of peak.
This is what makes semaglutide a true "weekly drug." With liraglutide's 13-hour half-life a missed daily dose drops plasma sharply; with semaglutide a 24-hour delay barely moves the curve. At steady state — reached after ~4–5 weeks — average plasma is roughly twice the single-dose Cmax. That accumulation drives semaglutide's sustained appetite and glucose effect, and it's why titration starts at 0.25 mg and steps up gradually.
The FDA Ozempic label specifies: if a dose is missed, take it within 5 days of the scheduled day; if more than 5 days have passed, skip it and resume the normal weekly schedule. The 5-day window exists because by then plasma levels have decayed enough that injecting could create an inconveniently shifted weekly cycle. The drug's long half-life buffers a single missed week.
Concretely: if you've been on 1 mg weekly for two months and skip a week, your plasma on the next scheduled dose day is near trough (~50% of peak); skipping further drops it to ~25% by the following week. Resuming a 1 mg dose lifts you back up, but full steady state takes 1–2 more weeks to re-establish. Most people don't notice a single skipped week symptomatically. They very much notice 3+ skipped weeks, when plasma falls below full GLP-1 receptor occupancy and appetite returns.
After your last semaglutide dose, plasma concentration follows the 7-day half-life decay shown in the table above. By 5 weeks (~35 days) the level is below 3% of peak — the standard pharmacological clearance threshold. Some clinicians cite 6–7 weeks for "complete" clearance to be safe. Behavioral effects (appetite, gastric emptying) typically return progressively over that window, not all at once.
Here's what a single 1 mg dose looks like over 5 weeks, as a simple text plot of relative plasma concentration:
| Day | Phase | Approx. % of peak |
|---|---|---|
| 0 | Injection (depot loading) | ~10% |
| 2 | Tmax — peak plasma | 100% |
| 9 | 1 half-life past peak | 50% |
| 16 | 2 half-lives | 25% |
| 23 | 3 half-lives | 12.5% |
| 30 | 4 half-lives | 6.25% |
| 37 | 5 half-lives — clinically cleared | 3.1% |
That decay assumes a single dose. If you stop after months at steady state, the curve starts from roughly twice the single-dose Cmax. The shape is identical but you're starting higher, so functional clearance from steady state is closer to 6 weeks. The FDA's GLP-1 safety communications note this prolonged tail in perioperative contexts.
Tirzepatide (Mounjaro for type 2 diabetes, Zepbound for weight management) has a half-life of ~120 hours, or ~5 days — shorter than semaglutide's 7 days but still long enough for once-weekly dosing. Full clearance after stopping takes roughly 25 days (5 × 5 days) versus 35 days for semaglutide. Both drugs use fatty-acid acylation for albumin binding; tirzepatide's slightly faster clearance reflects different linker chemistry.
Here is how the major GLP-1 and GLP-1/GIP/glucagon agonists compare:
| Compound (brand) | Half-life | Tmax | Bioavailability (SC) | Dosing |
|---|---|---|---|---|
| Semaglutide (Ozempic, Wegovy) | ~168 h (7 d) | ~48 h | 89% | Weekly |
| Tirzepatide (Mounjaro, Zepbound) | ~120 h (5 d) | ~36 h | 80% | Weekly |
| Dulaglutide (Trulicity) | ~120 h (5 d) | ~48 h | ~50% | Weekly |
| Liraglutide (Saxenda, Victoza) | ~13 h | ~10 h | 55% | Daily |
| Retatrutide (LY3437943) | ~144 h (6 d) | ~52 h | 85% | Weekly (trial) |
Sources: semaglutide and liraglutide values from FDA labels linked above; tirzepatide, dulaglutide, and retatrutide values from population-PK studies and FDA review documents, validated in Dose Track's parameter set (see supported medications). Liraglutide is the outlier — its 13-hour half-life is what forces daily dosing.
Dose Track charts this exact pharmacokinetic curve in real time, from your dose log. Log each Ozempic, Wegovy, Mounjaro, Trulicity, or Rybelsus injection and the app overlays peak, trough, and accumulation across weeks — so you can see steady state arrive, see a missed dose as a visible dip, and see the decay tail after stopping. See GLP-1 tracking features, the medications list, or download on the App Store.