One receptor or two
Both medicines copy gut hormones that the body releases after eating. Semaglutide is a GLP-1 receptor agonist; its labels describe a GLP-1 analogue with 94% sequence homology to human GLP-1 [1][2]. Tirzepatide is labelled as a GIP receptor and GLP-1 receptor agonist that binds to and activates both [3][4].
The labels describe the same broad effects: lower calorie intake, likely through appetite, insulin release and lower glucagon when blood sugar is high, and slower stomach emptying [1][3]. Both molecules carry a fatty acid chain that binds them to albumin in the blood, which slows their removal and allows weekly dosing [1][3].
Brands and approved uses in the US
- Ozempic® injection (semaglutide): type 2 diabetes in adults, plus lowering cardiovascular risk in adults with type 2 diabetes and established heart disease, and kidney risk when type 2 diabetes is accompanied by chronic kidney disease [1].
- Wegovy® injection and tablets (semaglutide): weight reduction and long-term maintenance, and lowering cardiovascular risk for adults whose obesity or overweight comes with established heart disease. The injection is also approved from age 12 for obesity and for a liver disease called MASH [2].
- Mounjaro® (tirzepatide): type 2 diabetes in adults and children aged 10 and older, and reducing major cardiovascular events in adults with type 2 diabetes at high risk [3].
- Zepbound® (tirzepatide): weight reduction and long-term maintenance in adults, and moderate to severe obstructive sleep apnoea in adults with obesity [4].
The US labels side by side
The table uses the same headings for both ingredients, and every entry comes from the label section named in the first column. Where only one brand gives a figure, the brand is named. A milligram of semaglutide and a milligram of tirzepatide are different amounts of different molecules, so the labels’ dose steps are left out on purpose [1][3].
| Label section | Semaglutide | Tirzepatide |
|---|---|---|
| Receptor targets (12.1) | GLP-1 receptor [1][2] | GIP and GLP-1 receptors [3][4] |
| Elimination half-life (12.3) | About 1 week [1][2] | About 5 days (Mounjaro®); about 5 to 6 days (Zepbound®) [3][4] |
| Time to peak after an injection (12.3) | 1 to 3 days [1][2] | 8 to 72 hours; median 24 hours in Zepbound® populations [3][4] |
| Steady state on weekly dosing (12.3) | After 4 to 5 weeks (Ozempic®) [1] | After 4 weeks [3][4] |
| Still in circulation after the last dose (12.3) | About 5 weeks (Ozempic®); 5 to 7 weeks (Wegovy®) [1][2] | No comparable figure in the labels [3][4] |
| Forms (3) | Weekly pens and single-dose syringes; daily tablets as Rybelsus®, Ozempic® tablets and Wegovy® tablets [1][2][5] | Weekly single-dose pens and vials, plus multi-dose KwikPen® and vials [3][4] |
| Missed weekly dose (2) | Ozempic®: within 5 days; Wegovy® injection: only if the next dose is more than 2 days away [1][2] | Within 4 days (96 hours) [3][4] |
| Moving the injection day (2) | At least 2 days between doses (Ozempic®) [1] | At least 3 days (72 hours) between doses [3][4] |
| Birth control pills (7, 8.3) | No instruction to change method [1][2] | Pill users are told to use another method, or a condom as well, for the first 4 weeks and the 4 weeks after every dose step [3][4] |
| Before a planned pregnancy (8.3) | Stop at least 2 months before [1][2] | No interval in the US labels; the EU Mounjaro® label says at least 1 month [3][4][6] |
| Boxed warning | Thyroid C-cell tumours in rodents [1][2] | The same warning [3][4] |
Why the timing rows differ
Half-life sets how long a medicine lingers. The Ozempic® label links its 2-month pregnancy rule to the long washout of semaglutide, and the Wegovy® label says semaglutide stays in the circulation for 5 to 7 weeks after the last dose [1][2]. The US tirzepatide labels give no comparable washout figure, while the EU product information for Mounjaro® asks for tirzepatide to be stopped at least a month before a planned pregnancy because of its long half-life [6].
The pill rule has a different basis. The tirzepatide labels tie it to delayed stomach emptying, which is greatest after the first dose and shrinks with time, so the advice covers the start of treatment and each step up [3][4]. The semaglutide injection labels contain no such instruction [1][2]. Any question about contraception or pregnancy planning on either medicine belongs with your prescriber.
Two head-to-head trials
Most comparisons rely on separate trials, each against placebo. Two randomised trials instead gave participants one medicine or the other. SURPASS-2 was run in type 2 diabetes and measured blood sugar control; SURMOUNT-5 was run in obesity without diabetes and measured weight [7][8]. The table sets them out under the same headings.
| SURPASS-2 (2021) | SURMOUNT-5 (2025) | |
|---|---|---|
| Who took part | 1,879 adults with type 2 diabetes on metformin [3][7] | 751 adults with obesity and no type 2 diabetes [8] |
| What was compared | Tirzepatide 5, 10 or 15 mg versus semaglutide 1 mg, weekly; 1 mg is an Ozempic® dose, below the usual 2.4 mg Wegovy® maintenance dose [1][2][7] | Highest tolerated tirzepatide (10 or 15 mg) versus highest tolerated semaglutide (1.7 or 2.4 mg), weekly [8] |
| Length and design | 40 weeks; open label, blinded only for the tirzepatide dose [3][7] | 72 weeks; phase 3b, open label [8] |
| Main outcome | Change in HbA1c [7] | Percent change in body weight [8] |
| Main result | HbA1c fell 2.01, 2.24 and 2.30 points with tirzepatide and 1.86 with semaglutide [7] | Weight changed −20.2% with tirzepatide and −13.7% with semaglutide [8] |
| Body size | Weight fell 1.9, 3.6 and 5.5 kg more with tirzepatide [7] | Waist shrank 18.4 cm with tirzepatide and 13.0 cm with semaglutide [8] |
| Side effects in the abstract | Nausea 17–22% vs 18%, diarrhoea 13–16% vs 12%, vomiting 6–10% vs 8% [7] | Mostly gastrointestinal and mild to moderate, mainly during dose escalation; no rates given [8] |
| Funding | Eli Lilly [7] | Eli Lilly [8] |
What the head-to-head trials leave open
- Both were open label: participants knew which medicine they were taking [7][8].
- Both were funded by Eli Lilly, the maker of tirzepatide [7][8].
- SURPASS-2 tested semaglutide 1 mg in type 2 diabetes, below the doses in the Wegovy® label for weight [2][7]. SURMOUNT-5 used semaglutide up to 2.4 mg; the Wegovy® label now also describes a 7.2 mg dose, which neither trial tested [2][8].
- The figures here come from the published abstracts and the Mounjaro® label; full papers report more detail on side effects and drop-outs.
- A group average does not predict one person’s result, side effects or tolerability.
Side effects as each label reports them
For the weight indications, each label has its own table of reactions that were more common than placebo in its own trials. The figures below are copied from those tables. The Wegovy® label points out that rates from one drug’s trials cannot be directly compared with another’s, so read each column only against its own placebo [2].
| Reaction | Wegovy® 2.4 mg vs placebo | Zepbound® 5 / 10 / 15 mg vs placebo |
|---|---|---|
| Nausea | 44 vs 16 [2] | 25 / 29 / 28 vs 8 [4] |
| Diarrhoea | 30 vs 16 [2] | 19 / 21 / 23 vs 8 [4] |
| Vomiting | 24 vs 6 [2] | 8 / 11 / 13 vs 2 [4] |
| Constipation | 24 vs 11 [2] | 17 / 14 / 11 vs 5 [4] |
| Abdominal pain | 20 vs 10 [2] | 9 / 9 / 10 vs 5 [4] |
Warnings they share
All four injection labels carry the boxed warning about thyroid C-cell tumours in rodents, and none of them is for someone with medullary thyroid carcinoma in their own or family history, or with MEN 2 [1][2][3][4]. They also share warnings on pancreatitis, gallbladder disease, low blood sugar with insulin or a sulfonylurea, kidney injury from dehydration, severe stomach reactions and aspiration during anaesthesia or deep sedation [1][3][4].
Using them together is not an option the labels allow: Wegovy® advises against combining it with other semaglutide products or any other GLP-1 receptor agonist, and Zepbound® says the same about other tirzepatide products and any GLP-1 receptor agonist [2][4].
Comparing your own weeks, not averages
If you move between these medicines, your prescriber decides how. What you can bring is a clear record: dose, date, injection site, appetite, stomach symptoms and weight, week by week.
Because the two half-lives differ, the date of the last dose of one and the first dose of the other is part of that record, and so is any planned surgery or procedure, which both labels ask you to mention in advance [1][4].
Ozempic®, Wegovy® and Rybelsus® are registered trademarks of Novo Nordisk A/S. Mounjaro®, Zepbound® and KwikPen® are registered trademarks of Eli Lilly and Company. PepLabo is not affiliated with or endorsed by Novo Nordisk or Eli Lilly and Company.
When to get help
| Sign | Who to contact | How fast | Source |
|---|---|---|---|
| Swelling of the face, lips, tongue or throat, or problems breathing after a dose | Stop the medicine and get emergency help | Emergency | Ozempic® Medication Guide [1]; Zepbound® section 17 [4] |
| Severe stomach pain that will not go away, sometimes spreading to the back | Stop the medicine and call your prescriber right away | Today | Ozempic® Medication Guide [1]; Zepbound® section 17 [4] |
| Upper stomach pain with fever or yellowing of the skin or eyes | Your prescriber, promptly | Today | Ozempic® Medication Guide, gallbladder [1] |
| Nausea, vomiting or diarrhoea that keeps going, with less urine or feeling dried out | Your prescriber, promptly | Today | Zepbound® section 17, acute kidney injury [4] |
| A planned operation, sedation or procedure | Tell the team doing it in advance | At your next appointment | Zepbound® section 17, aspiration [4] |
