Tirzepatide vs semaglutide: what the trials and labels show

The main difference between semaglutide and tirzepatide is how many hormone receptors each one activates. Semaglutide is a modified version of glucagon-like peptide-1 (GLP-1), a hormone the gut releases after eating. Its designers swapped two amino acids and attached a fatty-acid chain so that it binds to albumin in the blood and lasts about a week ^[1]. Tirzepatide is built on the sequence of a second gut hormone, glucose-dependent insulinotropic polypeptide (GIP), and activates both the GIP and the GLP-1 receptor ^{[2] [20]}. Eli Lilly developed it to test whether adding GIP activity would improve on GLP-1-only drugs.

Both are given as a once-weekly injection under the skin, both reduce appetite and slow stomach emptying, and both lower blood glucose in type 2 diabetes. The practical differences come from the trials: how much weight people lost, which conditions each drug is licensed for, and how the side effects compared. Each is covered below with the trial or label behind the figure. Both are prescription-only medicines, and whether either suits a particular person is a decision for their prescriber.

They belong to a wider family. The investigational drug retatrutide adds a third receptor, glucagon, and cagrilintide is an amylin analogue being studied in combination with semaglutide. Neither is licensed.

Four brand names account for most searches. Ozempic and Wegovy both contain semaglutide and are made by Novo Nordisk. In the US, Ozempic is licensed for type 2 diabetes, including reducing cardiovascular and kidney risks in adults with diabetes ^[18]. Wegovy is licensed for weight management, for reducing the risk of heart attack and stroke in adults with established cardiovascular disease and obesity or overweight, and, under accelerated approval, for a form of fatty liver disease (MASH) with moderate to advanced fibrosis. Wegovy is also approved in the US as a once-daily tablet ^[17].

Mounjaro and Zepbound both contain tirzepatide and are made by Eli Lilly. In the US, Mounjaro is licensed for type 2 diabetes in adults and in children aged 10 and over, and its current label adds reducing the risk of major cardiovascular events in adults with type 2 diabetes who are at high risk of them ^[20]. Zepbound is the US brand for weight management and for moderate to severe obstructive sleep apnoea in adults with obesity ^[19].

So, is Zepbound a semaglutide? No: Zepbound is tirzepatide. Is Mounjaro semaglutide? Also no; Mounjaro is tirzepatide too. The UK uses fewer names. The MHRA lists Wegovy (semaglutide) as licensed for weight management, Ozempic and Rybelsus (semaglutide) for diabetes, and Mounjaro (tirzepatide) for both diabetes and weight management ^[21]. A UK search for semaglutide vs Mounjaro is therefore the same question as tirzepatide vs semaglutide. The same goes for tirzepatide vs Ozempic and tirzepatide vs Wegovy, with one caveat: Ozempic is used at lower diabetes doses than Wegovy.

At the GLP-1 receptor both drugs have the same broad effects: more insulin and less glucagon when blood glucose is raised, slower stomach emptying, and reduced appetite through action in the brain. The US labels describe tirzepatide as selectively binding and activating both the GIP and GLP-1 receptors, and semaglutide as a GLP-1 receptor agonist whose long action comes mainly from albumin binding ^{[20] [18]}.

What GIP activity adds is still debated. In Lilly’s discovery work, tirzepatide reduced body weight and food intake in mice more than a selective GLP-1 agonist, and early human studies supported once-weekly dosing ^[2]. The clinical comparisons are more informative than the theory: in both head-to-head trials described below, tirzepatide lowered weight more than semaglutide ^{[3] [6]}.

The two also leave the body at different speeds. The US labels give an elimination half-life of about 1 week for semaglutide, which stays in the circulation for about 5 weeks after the last dose, and about 5 days for tirzepatide ^{[18] [20]}. The Wegovy label ties its advice to stop at least 2 months before a planned pregnancy to semaglutide’s long half-life; the MHRA gives at least 1 month for tirzepatide ^{[17] [21]}.

SURMOUNT-5 is the only published trial that has compared the two drugs directly for obesity. It enrolled 751 adults with obesity but without type 2 diabetes. They were randomly assigned to the maximum tolerated dose of tirzepatide (10 mg or 15 mg) or of semaglutide (1.7 mg or 2.4 mg), injected once weekly for 72 weeks. The trial was open-label, so participants knew which drug they were taking, and it was funded by Eli Lilly, which makes tirzepatide ^[3].

Average weight change at 72 weeks was a loss of 20.2% with tirzepatide and 13.7% with semaglutide. Waist circumference fell by 18.4 cm against 13.0 cm. Participants on tirzepatide were more likely to reach every weight-loss threshold the trial measured, from 10% up to 25% of body weight. In both groups the most common adverse events were gastrointestinal, mostly mild to moderate, and mainly during the dose-escalation period ^[3].

These results answer the head-to-head question for one population: adults with obesity and without diabetes, over 72 weeks, at the highest dose each person tolerated. They do not show how the drugs compare at lower doses, in people with diabetes, or on outcomes such as heart attacks, which the trial was not designed to measure.

Before SURMOUNT-5, most comparisons of semaglutide and tirzepatide set their separate placebo-controlled trials next to each other. In STEP 1, 1,961 adults without diabetes took semaglutide 2.4 mg or placebo weekly for 68 weeks alongside lifestyle advice. Average weight fell by 14.9% on semaglutide against 2.4% on placebo, and 50.5% of the semaglutide group lost at least 15% of their body weight ^[4].

In SURMOUNT-1, 2,539 adults without diabetes took tirzepatide 5 mg, 10 mg or 15 mg or placebo weekly for 72 weeks, including a 20-week dose-escalation period. Average weight fell by 15.0%, 19.5% and 20.9% on the three doses against 3.1% on placebo, and 57% of the 15 mg group lost at least 20% of their body weight ^[5].

Comparisons across separate trials need care, because the trials differed in length, participants and methods. A 2026 network meta-analysis in BMJ Medicine pooled 58 randomised trials in adults with overweight or obesity and without diabetes. It estimated weight loss 19.28 percentage points greater than placebo for tirzepatide, while conventional GLP-1 drugs, the group that includes semaglutide, showed more modest effects. The authors noted limited head-to-head evidence and overlapping confidence intervals for several comparisons ^[13].

In type 2 diabetes the direct comparison is SURPASS-2. It randomised 1,879 adults to tirzepatide 5 mg, 10 mg or 15 mg or to semaglutide 1 mg, an Ozempic dose, for 40 weeks. HbA1c fell by 2.01, 2.24 and 2.30 percentage points on the three tirzepatide doses against 1.86 points on semaglutide, and every tirzepatide dose was superior on this measure. Weight reductions were greater with tirzepatide by 1.9 kg, 3.6 kg and 5.5 kg ^[6].

Nausea was reported by 17% to 22% of people on tirzepatide and 18% on semaglutide, diarrhoea by 13% to 16% and 12%, and vomiting by 6% to 10% and 8%. Low blood glucose below 54 mg/dL was uncommon in every group. Serious adverse events were reported in 5% to 7% of the tirzepatide groups and 3% of the semaglutide group ^[6]. The current US Ozempic label allows up to 2 mg weekly, a dose SURPASS-2 did not test ^[18].

The two drugs have outcome evidence in different areas. In SELECT, 17,604 adults with cardiovascular disease and overweight or obesity but without diabetes had fewer major cardiovascular events on semaglutide 2.4 mg weekly than on placebo (6.5% against 8.0%) ^[9]. In FLOW, semaglutide 1 mg lowered the risk of major kidney disease events by 24% in people with type 2 diabetes and chronic kidney disease ^[10]. Wegovy’s cardiovascular indication and Ozempic’s kidney indication in the US rest on this kind of evidence ^{[17] [18]}.

Tirzepatide’s outcome trials include SURMOUNT-OSA, in which it reduced sleep apnoea events by about 20 to 24 more per hour than placebo ^[11], and SUMMIT. In SUMMIT, cardiovascular death or worsening heart failure occurred in 9.9% on tirzepatide against 15.3% on placebo in people with heart failure with preserved ejection fraction and obesity ^[12]. The US Mounjaro label also carries a cardiovascular risk-reduction indication for adults with type 2 diabetes at high risk ^[20]. No published trial has compared the two drugs on heart or kidney outcomes.

The side-effect profiles are similar in kind. Both US labels list nausea, diarrhoea, vomiting and constipation among the most common adverse reactions, mainly during dose increases. Both carry a boxed warning because the drugs caused thyroid C-cell tumours in rodents; whether this happens in humans is not known, and both are contraindicated in people with a personal or family history of medullary thyroid carcinoma or MEN 2 ^{[17] [19]}. Both labels also warn about acute pancreatitis, gallbladder disease, kidney injury from dehydration, serious allergic reactions, eye complications in people with diabetic retinopathy, and aspiration during anaesthesia or deep sedation ^{[17] [19]}.

The rates printed on each label come from different trials, so they cannot be compared directly. In the pooled Wegovy weight-management trials, nausea was reported by 44% on semaglutide 2.4 mg against 16% on placebo ^[17]. In the pooled Zepbound trials, nausea was reported by 25% to 29% on 5 mg to 15 mg against 8% on placebo ^[19]. The direct comparisons are more reliable. In SURPASS-2, nausea rates were close (17% to 22% against 18%) ^[6], and in SURMOUNT-5 the pattern of mostly mild to moderate gastrointestinal events was similar in both groups ^[3].

A few points are specific to one drug. The tirzepatide labels advise people who use oral contraceptives to change to a non-oral method, or add a barrier method, for 4 weeks after starting and after each dose increase, because tirzepatide may reduce how well the pill works ^{[19] [21]}. The Wegovy label includes a warning about increased heart rate ^[17]. The MHRA notes very rare reports linking semaglutide to an eye condition called non-arteritic anterior ischaemic optic neuropathy (NAION) and says it is reviewing evidence for other GLP-1 medicines ^[21].

Stopping because of side effects was uncommon but not rare in the pivotal trials. In SURMOUNT-1, 4.3% to 7.1% of tirzepatide users stopped treatment because of adverse events, against 2.6% on placebo ^[5]. In STEP 1, 4.5% of semaglutide users stopped because of gastrointestinal events, against 0.8% on placebo ^[4].

On the measures tested head to head, the trials favour tirzepatide. For weight loss in adults without diabetes, SURMOUNT-5 found 20.2% against 13.7% ^[3]. For blood glucose in type 2 diabetes, SURPASS-2 found larger HbA1c reductions than with semaglutide 1 mg ^[6].

Asking whether tirzepatide is better than semaglutide for a particular person is a different question. Semaglutide has a completed cardiovascular outcome trial in people without diabetes ^[9], a licensed tablet form, and US indications that tirzepatide does not have, such as MASH ^[17]. Tirzepatide has indications that semaglutide does not, such as obstructive sleep apnoea in the US ^[19]. Medical history, tolerability and availability differ between people and health systems, which is why the choice sits with a prescriber.

The doses below are those studied in trials or approved on labels. They are reported for information, not as a recommendation. Semaglutide for weight management was studied at 2.4 mg once weekly in STEP 1 and SELECT ^{[4] [9]}. The current US Wegovy label starts the injection at 0.25 mg weekly, increases it gradually, and gives maintenance doses of 1.7 mg or 2.4 mg, with a maximum of 7.2 mg weekly for weight reduction in some adults ^[17]. Ozempic, for diabetes, is labelled at maintenance doses of 0.5 mg, 1 mg or 2 mg weekly ^[18].

Tirzepatide was studied at 5 mg, 10 mg and 15 mg weekly in SURMOUNT-1 and SURPASS-2 ^{[5] [6]}. The US Zepbound label starts at 2.5 mg weekly, a dose used only to begin treatment, and gives maintenance doses of 5 mg, 10 mg or 15 mg for weight management and 10 mg or 15 mg for sleep apnoea ^[19]. Mounjaro has the same starting dose and a maximum of 15 mg weekly in adults ^[20].

The milligram figures are not interchangeable. Semaglutide and tirzepatide are different molecules with different potencies, and neither label offers a conversion from one to the other.

Switching from semaglutide to tirzepatide has not been tested in a randomised trial. The US tirzepatide labels contain no conversion from semaglutide, and the Zepbound label states that using it together with any GLP-1 receptor agonist is not recommended ^{[19] [20]}.

The published evidence on switching is small and observational. A Japanese retrospective study followed 15 people with type 2 diabetes who moved from semaglutide 1 mg to tirzepatide because of inadequate weight loss. All started tirzepatide at 2.5 mg, and over 3 months those who went on to 10 mg had a significant fall in HbA1c ^[14]. A single-centre study of 11 people who moved from oral semaglutide to tirzepatide reported better treatment-related quality-of-life scores after 3 months, with no significant change in HbA1c or weight ^[15]. Studies this small cannot show whether switching works better than staying on semaglutide.

The MHRA advises consulting a healthcare professional before switching from one GLP-1 medicine to another, including between brands of the same drug. It notes that the medicines differ in strength and use, and that switching without advice may increase side effects or make treatment less effective ^[21].

Both drugs have randomised withdrawal trials, and they point the same way. In STEP 4, people who had lost 10.6% of their weight on semaglutide over 20 weeks and were then switched to placebo regained 6.9% over the next 48 weeks, while those who continued lost a further 7.9% ^[7]. In SURMOUNT-4, people who had lost 20.9% over 36 weeks on tirzepatide and were then switched to placebo regained 14.0% over 52 weeks, while those who continued lost a further 5.5% ^[8].

Semaglutide and tirzepatide are licensed prescription-only medicines in the UK. The MHRA says that selling them through unregulated channels is against the law, that licensed GLP-1 medicines come as prefilled pens or tablets, and that powder in vials that must be mixed before injection is not authorised ^[21]. In the US, the FDA has warned about companies selling semaglutide and tirzepatide falsely labelled as being for research purposes ^[22]. Our UK legal status and US legal status pages summarise the wider rules.

Unlicensed products are not the medicines studied in these trials. In a 2024 study of semaglutide ordered from illegal online pharmacies, all three vials that arrived were judged probably substandard or falsified: measured purity was 7.7% to 14.4% against a claimed 99%, and bacterial endotoxin was found in every sample. None of the three Ozempic pens ordered was delivered ^[16]. Our guides to spotting a fake supplier, third-party testing and reading a certificate of analysis explain what independent testing can and cannot confirm.

PepFinder does not sell either peptide. Supplier listings we track for research-labelled material are on the semaglutide and tirzepatide price pages. How we assess suppliers is set out in our methodology, and nothing on this page is medical advice (see our disclaimer).