Pick a medication
Move through the weeks
Medication in the blood
percent of its own steady level
Stop after four doses
Runs the same weeks with the last injection given on day 21, so you can see how long the medication stays in the body once it is stopped.
Where the medication goes, and what it does there
Tap any stop to read what happens there. A filled dot means this medication acts at that place.
The curve is a standard one-compartment model built from the two labels' own published numbers: absorption from under the skin, a peak at one to three days for semaglutide and a median of 24 hours for tirzepatide, and an elimination half-life of about a week for semaglutide and about five to six days for tirzepatide. Each line is scaled to its own steady level, so the shapes can be compared with each other while the amounts cannot. A milligram of one is not a milligram of the other and the two are never plotted on a shared amount scale here. The model also holds the dose constant. In real life the dose goes up every four weeks during titration, so the level keeps climbing for longer than this shows. Nothing here predicts your own blood levels.
What they are
Both are peptides, which means short protein chains, and both are made to look enough like a natural hormone that your receptors answer them. Native GLP-1 is broken down within a couple of minutes by an enzyme called DPP-4. Both medications are built to get around that, and both hold on to albumin, the most common protein in blood, which keeps them in circulation and out of the kidneys. That is the whole reason a once-weekly shot is possible. The numbers below come from the current FDA labels.
One receptor
Semaglutide
Sold as Wegovy and Ozempic
- What it copies
- Human GLP-1, with 94% of the same sequence. It binds the GLP-1 receptor, the target of the hormone your own gut releases with a meal.
- What was changed
- Position 8 was altered so DPP-4 cannot cut it. A C18 fatty diacid was attached to lysine 26 through a spacer, which is what makes it stick to albumin.
- Size
- 4,113.58 g/mol. For scale, orforglipron, the new GLP-1 that works as an ordinary pill, weighs 902 g/mol.
- After the shot
- 89% of the dose reaches the blood. Peak at 1 to 3 days. Half-life about 1 week, and it is still in circulation 5 to 7 weeks after the last dose.
- Dose ladder
- 0.25 mg, then 0.5, 1, 1.7 and 2.4 mg, four weeks at each step. For weight, it can go to 7.2 mg after at least four weeks at 2.4 mg.
Two receptors
Tirzepatide
Sold as Zepbound and Mounjaro
- What it copies
- It is built on the GIP sequence, the other hormone the gut releases with food, and it activates both the GIP receptor and the GLP-1 receptor.
- What was changed
- Two positions carry a synthetic amino acid that blocks DPP-4, the tail end is capped, and a C20 fatty diacid is attached at lysine 20 for albumin binding.
- Size
- 4,813.53 Da, a slightly longer chain than semaglutide with a longer fatty tail.
- After the shot
- 80% of the dose reaches the blood. Peak at a median of 24 hours, anywhere from 8 to 72. Half-life about 5 to 6 days, steady after 4 weeks of weekly dosing.
- Dose ladder
- 2.5 mg for four weeks, then 5 mg, then 2.5 mg more at a time no sooner than every four weeks, to a maximum of 15 mg.
Neither one is insulin, and neither one is a stimulant. They do not burn anything. They occupy receptors that already exist in your body and that already run appetite, stomach emptying and the pancreas response to a meal.
Why it is a shot and not a pill
A peptide swallowed as an ordinary tablet is treated by the body as food. Stomach acid and protein-digesting enzymes take it apart before it can reach the blood. Injecting under the skin skips all of that, which is why the injection delivers 89% of a semaglutide dose and 80% of a tirzepatide dose into circulation.
Under the skin the dose does not rush in. It sits in the fat as a small reservoir and moves into the blood over days, which is the first half of why the level climbs slowly on the chart above. The labels for both medications report the same exposure whether the injection goes in the abdomen, the thigh or the upper arm, so the site is a comfort and rotation decision rather than a dosing one.
There are now oral versions that get around the digestion problem in two completely different ways, one with an absorption helper called SNAC and one by not being a peptide at all. That is a separate tool, and it is the one to read before judging anything sold online as an oral or under-the-tongue version of these medications.
What the second receptor adds
This is the honest centre of the difference between the two, and it is less settled than the marketing suggests. GLP-1 and GIP are both released by the gut when food arrives. Semaglutide works on one of them. Tirzepatide works on both. What the GIP half contributes is still being worked out, and the label says so in plain words.
What the label claims
Zepbound's label states that GIP and GLP-1 receptors are both found in areas of the brain involved in appetite, and that nonclinical studies suggest the addition of GIP may further contribute to the regulation of food intake. That word is the label's own. It also reports something semaglutide's label does not claim: measured on a hyperinsulinemic euglycemic clamp after 28 weeks, tirzepatide increased insulin sensitivity.
What the head-to-head found
SURMOUNT-5 put the two against each other directly in 751 adults with obesity and without diabetes, for 72 weeks, each titrated to the highest dose they could tolerate. Tirzepatide averaged 20.2% of body weight lost and semaglutide 13.7%. That trial ran before the 7.2 mg semaglutide dose existed, so it compared tirzepatide's ceiling with a 2.4 mg semaglutide ceiling.
The averages are not a forecast for one person. In the same trials, a large share of people on semaglutide lost more than the tirzepatide average and a share of people on tirzepatide lost very little. Tolerance matters more than the ranking: the medication you can actually stay on at a full dose beats the one that looks better on a chart and makes you too sick to take.
What the trials measured
Average percentage of body weight lost, from the FDA labels for each medication. Every row is a different trial with different people, so the only fair comparison in this table is the last row, where the two were tested against each other.
| Trial | Medication and dose | Length | Average weight change | Placebo |
|---|---|---|---|---|
| Wegovy label, Study 2 | Semaglutide 2.4 mg weekly | 68 weeks | −14.9% | −2.4% |
| Wegovy label, Study 8 | Semaglutide 7.2 mg weekly | 72 weeks | −18.8% | −3.9% |
| Wegovy label, Study 8 | Semaglutide 2.4 mg, same trial | 72 weeks | −15.5% | −3.9% |
| Zepbound label, Study 1 | Tirzepatide 5 mg weekly | 72 weeks | −15.0% | −3.1% |
| Zepbound label, Study 1 | Tirzepatide 10 mg weekly | 72 weeks | −19.5% | −3.1% |
| Zepbound label, Study 1 | Tirzepatide 15 mg weekly | 72 weeks | −20.9% | −3.1% |
| SURMOUNT-5, head to head | Tirzepatide vs semaglutide, max tolerated | 72 weeks | −20.2% vs −13.7% | no placebo arm |
All figures are the intention-to-treat results, meaning everyone who was randomised counts, including people who stopped early. Company announcements often quote a second, higher number for people who stayed on the medication the whole time. Both are real, they answer different questions, and the lower one is the one that includes the people it did not work out for.
Why the dose climbs so slowly
Both labels say the escalation exists to reduce gastrointestinal side effects, not to build up an effect. Nausea is the most common reaction to both: on semaglutide 2.4 mg it was reported by 44% against 16% on placebo, and on tirzepatide by 25% to 29% depending on dose against 8% on placebo. Those come from separate trials with different people, and both labels warn in their own text that rates from one drug's trials cannot be compared directly with another's.
The chart above shows the second reason a slow start makes sense. Because each dose lasts longer than a week, the level does not reset between injections. It stacks, and it keeps rising for about four to five weeks before it levels off. The dose you take in week one is still partly present in week three. Going up before the previous step has settled means raising a level that was still climbing on its own.
The same arithmetic runs backwards at the end. Semaglutide is still in circulation five to seven weeks after the last dose, so stopping is a slow fade rather than a switch, and side effects that are dose related fade on the same slow schedule.
Four things this tool does not show
Your own levels
The curve is a model of the average published behaviour of each medication, not a measurement. Real people absorb and clear at different rates, and nobody is measuring these levels in ordinary care.
The titration you are actually on
The model holds one dose steady across eight weeks. A real start raises the dose every four weeks, so the true line steps up several times before it flattens.
What the receptors feel like
A blood level is not appetite. The response to the same level varies a great deal between people, which is why two people on the same dose can have very different weeks.
Everything else in the label
Both carry a boxed warning about thyroid C-cell tumours seen in rodents, and both have real contraindications and interactions. This is a mechanism tool, not a safety summary. Read the label and talk to your prescriber.
Not medical advice
Nothing here is a recommendation for or against either medication, and neither one is better than the other in the abstract. Dose, tolerance, coverage, supply and your own health history decide that, and those are conversations for your prescriber.
Sources
6 references
- Wegovy (semaglutide) Prescribing Information. Novo Nordisk. Current label at DailyMed. Source for 94% sequence homology with human GLP-1, the position 8 modification against DPP-4 and the C18 fatty diacid at lysine 26, the molecular weight of 4,113.58 g/mol, 89% absolute bioavailability, a peak at 1 to 3 days, greater than 99% albumin binding, a half-life of about one week with the medication present for 5 to 7 weeks after the last dose, equal exposure from the abdomen, thigh or upper arm, the dose ladder to 2.4 mg and the 7.2 mg option for weight, the Study 2 and Study 8 weight results, and the 44% nausea figure.
- Zepbound (tirzepatide) Prescribing Information. Eli Lilly. Current label at DailyMed. Source for tirzepatide being built on the GIP sequence with aminoisobutyric acid at positions 2 and 13 and a C20 fatty diacid at lysine 20, the molecular weight of 4,813.53 Da, 80% bioavailability, a median peak at 24 hours with a range of 8 to 72, 99% albumin binding, a half-life of 5 to 6 days and steady state after 4 weeks, the wording that nonclinical studies suggest GIP may further contribute to the regulation of food intake, the clamp study showing increased insulin sensitivity, the gastric emptying delay being largest after the first dose, the dose ladder to 15 mg, the Study 1 weight results, and the nausea figures by dose.
- Aronne LJ, Horn DB, le Roux CW, et al. Tirzepatide as compared with semaglutide for the treatment of obesity (SURMOUNT-5). New England Journal of Medicine. 2025;393(1):26–36. doi:10.1056/NEJMoa2416394. The only head-to-head trial of the two, and the source of the 20.2% and 13.7% figures at 72 weeks in 751 adults.
- Wilding JPH, et al. Once-weekly semaglutide in adults with overweight or obesity (STEP 1). New England Journal of Medicine. 2021;384(11):989–1002. doi:10.1056/NEJMoa2032183. The published trial behind the label's Study 2 result.
- Jastreboff AM, et al. Tirzepatide once weekly for the treatment of obesity (SURMOUNT-1). New England Journal of Medicine. 2022;387(3):205–216. doi:10.1056/NEJMoa2206038. The published trial behind the label's Study 1 result.
- Campbell JE, Drucker DJ. Pharmacology, physiology, and mechanisms of incretin hormone action. Cell Metabolism. 2013;17(6):819–837. doi:10.1016/j.cmet.2013.04.008. Source for native GLP-1 being cleared within minutes by DPP-4, and for insulin release and glucagon suppression being glucose dependent.