Peptio

Tirzepatide

Also known as LY3298176, Mounjaro, Zepbound

Tirzepatide is a dual GIP and GLP-1 receptor agonist, approved in the US and the EU for type 2 diabetes and for weight management.

Tirzepatide is a single synthetic peptide that activates two receptors, the ones the body's own GIP and GLP-1 act on. Eli Lilly developed it under the code LY3298176. It is an approved medicine. In the US it is sold as Mounjaro for type 2 diabetes and as Zepbound for weight management and obstructive sleep apnoea. In the EU it is authorised as Mounjaro alone, which there covers both type 2 diabetes and weight management.

What it is

The US Zepbound label describes tirzepatide as based on the GIP sequence, with aminoisobutyric acid (Aib) at positions 2 and 13, a C-terminal amide, and a lysine at position 20 attached through a linker to a 20-carbon fatty diacid. The label says that fatty diacid lets the molecule bind albumin and prolongs its half-life.

Aib is not one of the twenty amino acids the genetic code specifies, and the fatty-acid chain is not an amino acid at all. No sequence written in the twenty standard one-letter codes can describe that structure, which is why none is shown on this page. The molecular weight given here, 4813.53, and the formula C225H348N48O68 are the label's own.

Where it is approved

In the US, tirzepatide is approved under two brand names, each with its own application, both Lilly's. Each date below is from the electronic signature page of FDA's letter.

  • Mounjaro was approved on 13 May 2022 to improve glycaemic control in adults with type 2 diabetes (approval letter).
  • Zepbound was approved on 8 November 2023 for chronic weight management in adults (approval letter). The current label words this as reducing excess body weight and maintaining weight reduction long term.
  • Zepbound gained moderate to severe obstructive sleep apnoea in adults with obesity on 20 December 2024 (supplement approval letter).
  • Mounjaro was extended to children aged 10 and older with type 2 diabetes on 19 December 2025 (supplement approval letter).
  • Mounjaro gained reduction of the risk of major adverse cardiovascular events, meaning cardiovascular death, non-fatal heart attack or non-fatal stroke, in adults with type 2 diabetes at high risk of them, on 27 August 2026 (supplement approval letter).

In the EU, tirzepatide is authorised only as Mounjaro. EMA's product information gives its date of first authorisation as 15 September 2022 and lists two indications: type 2 diabetes in adults, adolescents and children aged 10 and above, and weight management in adults. It does not say when the weight management indication was added. It refers readers to trial results in obstructive sleep apnoea and in heart failure with preserved ejection fraction, but lists neither as an indication. Heart failure is not an indication on either US label. Only FDA and EMA were checked for this page; other regulators were not.

The thyroid warning, and where the US and the EU differ

Both US labels carry a boxed warning. In rats, tirzepatide causes thyroid C-cell tumours that increase with dose and with length of treatment, at clinically relevant exposures. It is unknown whether it causes such tumours, including medullary thyroid carcinoma, in humans, because the human relevance of the rat finding has not been determined. Both US labels contraindicate tirzepatide in people with a personal or family history of medullary thyroid carcinoma or with multiple endocrine neoplasia syndrome type 2 (MEN 2), and in people with known serious hypersensitivity to it.

The EU takes a different position. The EU product information's only contraindication is hypersensitivity to the active substance or its excipients. It reports the rat finding, an increase in thyroid C-cell adenomas and carcinomas at all doses compared with controls, and says: "The human relevance of these findings is unknown." The thyroid contraindication is a US position, not a universal one.

The thyroid finding is not the only warning. Both US labels also carry warnings and precautions on, among other things, pancreatitis, gallbladder disease, hypoglycaemia, acute kidney injury, diabetic retinopathy complications in people with type 2 diabetes, and pulmonary aspiration during anaesthesia or deep sedation. The Zepbound label lists among its recent major changes: "Suicidal Behavior and Ideation (Removed) 02/2026". On pregnancy, its highlights state "May cause fetal harm", and the EU product information reports malformations in rats and foetal growth reductions in rats and rabbits.

What is not known

There is no result on major adverse cardiovascular events for tirzepatide in people with obesity who do not have diabetes. The heart failure trial SUMMIT, described above, measured a different outcome, cardiovascular death or worsening heart failure, in people who already had heart failure. The trial built to find out, SURMOUNT-MMO, is recorded as active and not recruiting, with primary completion estimated for October 2027.

The only published trial of major adverse cardiovascular events, SURPASS-CVOT, compared tirzepatide with dulaglutide, not with placebo, and only in people with type 2 diabetes and atherosclerotic cardiovascular disease. It showed tirzepatide was not worse. It did not show it was better.

Whether the thyroid tumours seen in rats matter for people is unknown, in the words of both regulators. FDA's Zepbound approval letter requires a registry-based case series of medullary thyroid carcinoma lasting at least 15 years, with completion scheduled for August 2040.

The withdrawal trial followed people for 52 weeks after they stopped. Nothing on this page describes what happens after that. Every trial on this page was funded by Lilly.

Compounded and "research" tirzepatide

Tirzepatide injection was on FDA's drug shortage list from 15 December 2022. In a declaratory order dated 19 December 2024, FDA determined that the shortage was resolved. FDA's page on its compounding policies gives the end of the grace periods that followed: 18 February 2025 for state-licensed pharmacies compounding under section 503A of the FD&C Act, and 19 March 2025 for outsourcing facilities under section 503B. The same page, current as of 1 April 2026, says tirzepatide does not appear on FDA's drug shortage list or on the 503B bulks list.

FDA states that as of 31 May 2026 it had received more than 730 reports of adverse events associated with compounded tirzepatide. It adds that it is not always possible to determine whether an adverse event resulted from the drug or whether other factors contributed, and that such events are likely under-reported, because federal law does not require state-licensed pharmacies that are not outsourcing facilities to report them.

The same page says FDA has warned companies that illegally sold unapproved drugs containing tirzepatide, semaglutide, retatrutide and others that were "falsely labeled 'for research purposes' or 'not for human consumption.'" Tirzepatide is named in a February 2025 warning letter, one in March 2026 and another in August 2026. In the first, FDA found that despite statements such as "research use only" and "not for human consumption" on the labelling and website, evidence from the website established that certain of its products were drugs intended for human use.

Every trial result on this page describes Lilly's product given under trial conditions. None of it describes a compounded product or one sold for research use.

Anti-doping

WADA's Prohibited List could not be retrieved for this page, so the page says nothing about tirzepatide's status in sport, in either direction.

What the research shows

Each statement below is labelled with the strongest kind of study supporting it, and links to that study.

  • Human randomised trialSupportive / High confidence

    In a phase 3 trial of 2539 adults with obesity, or overweight with a weight-related complication, and without diabetes, body weight fell more with tirzepatide than with placebo over 72 weeks.

    SURMOUNT-1 randomised 2539 adults with a BMI of 30 or more, or 27 or more with at least one weight-related complication, and without diabetes, in a 1:1:1:1 ratio to tirzepatide at 5 mg, 10 mg or 15 mg, or to placebo, for 72 weeks. At baseline, mean body weight was 104.8 kg and mean BMI 38.0. Under the treatment-regimen estimand, which assessed effects regardless of whether participants stopped treatment, in the intention-to-treat population, mean body weight at week 72 changed by -15.0%, -19.5% and -20.9% in the three arms against -3.1% with placebo. A reduction of 5% or more was reached by 85%, 89% and 91% of participants against 35% with placebo, and a reduction of 20% or more by 50% in the 10 mg arm and 57% in the 15 mg arm against 3% with placebo.

    Tested in humans under randomised, controlled conditions.

    • The figures come from the published abstract only. The full text was not read for this page.
    • The trial was funded by Eli Lilly, the developer.
    • The results describe Lilly's product given under trial conditions. They do not describe compounded tirzepatide or any product sold for research use.
    • The abstract states no difference from placebo in percentage points and gives no efficacy-estimand result.
    • The abstract gives the allocation ratio, not the number of participants in each arm, and gives no figure for the 5 mg arm on a reduction of 20% or more.

    PMID 35658024

  • Human randomised trialSupportive / High confidence

    In a phase 3 trial of 938 adults with type 2 diabetes and a BMI of 27 or higher, body weight fell more with tirzepatide than with placebo over 72 weeks.

    SURMOUNT-2 enrolled adults with a BMI of 27 or higher and type 2 diabetes with a glycated haemoglobin (HbA1c) of 7% to 10%. Of these, 938 were randomised and received at least one dose of tirzepatide 10 mg (312), tirzepatide 15 mg (311) or placebo (315), for 72 weeks. Mean age was 54.2 years. Under the treatment-regimen estimand, which assessed effects regardless of stopping treatment or starting rescue diabetes medicine, mean body weight at week 72 changed by -12.8% with 10 mg and -14.7% with 15 mg against -3.2% with placebo, estimated differences of -9.6 and -11.6 percentage points. A reduction of 5% or more was reached by 79 to 83% of participants on tirzepatide against 32% on placebo.

    Tested in humans under randomised, controlled conditions.

    • Two participants in the 10 mg group died. The investigator did not consider either death related to the study treatment.
    • The figures come from the published abstract only. The full text was not read for this page.
    • The trial was funded by Eli Lilly, the developer.
    • The results describe Lilly's product given under trial conditions. They do not describe compounded tirzepatide or any product sold for research use.
    • The trial had no 5 mg arm.
    • The abstract gives no efficacy-estimand result.

    PMID 37385275

  • Human randomised trialSupportive / High confidence

    In a randomised withdrawal trial in adults with obesity or overweight and without diabetes, people switched to placebo regained weight over 52 weeks, while people who continued tirzepatide lost more.

    SURMOUNT-4 enrolled 783 adults with a BMI of 30 or more, or 27 or more with a weight-related complication, and without diabetes, at 70 sites in 4 countries. All first received tirzepatide at their maximum tolerated dose, 10 mg or 15 mg, in a 36-week open-label lead-in. The 670 of the 783 who completed the lead-in, and who had lost a mean 20.9% of their weight by then, were randomised in a double-blind phase to continue tirzepatide (335) or switch to placebo (335) for 52 weeks. From week 36 to week 88, mean body weight changed by -5.5% with tirzepatide and rose by 14.0% with placebo, a difference of -19.4 percentage points (95% CI -21.2 to -17.7). At week 88, 300 participants (89.5%) on tirzepatide had kept at least 80% of the weight lost in the lead-in, against 16.6% on placebo. Over the whole 88 weeks, mean weight fell by 25.3% in the tirzepatide group and 9.9% in the placebo group.

    Tested in humans under randomised, controlled conditions.

    • The figures come from the published abstract only. The full text was not available when this page was written.
    • The trial was sponsored by Eli Lilly, the developer, according to its registry record (ClinicalTrials.gov NCT04660643). The abstract carries no funding statement.
    • The results describe Lilly's product given under trial conditions. They do not describe compounded tirzepatide or any product sold for research use.
    • The abstract names no estimand.
    • The abstract prints the placebo figure as 14.0% without a sign. Its conclusion describes this as substantial regain of lost weight.
    • Only people who completed 36 weeks on tirzepatide were randomised, so the 25.3% overall figure describes that group and cannot be compared with SURMOUNT-1's figures.
    • Follow-up after withdrawal lasted 52 weeks. What happens to weight beyond that is not known from this trial.

    PMID 38078870

  • Human randomised trialSupportive / Moderate confidence

    In an open-label trial of 751 adults with obesity and without type 2 diabetes, body weight fell more with tirzepatide than with semaglutide over 72 weeks.

    SURMOUNT-5, a phase 3b trial, randomised 751 adults with obesity but without type 2 diabetes in a 1:1 ratio to the maximum tolerated dose of tirzepatide (10 mg or 15 mg) or the maximum tolerated dose of semaglutide (1.7 mg or 2.4 mg), for 72 weeks. The least-squares mean change in body weight at week 72 was -20.2% (95% CI -21.4 to -19.1) with tirzepatide and -13.7% (95% CI -14.9 to -12.6) with semaglutide. Waist circumference changed by -18.4 cm with tirzepatide and -13.0 cm with semaglutide. Participants on tirzepatide were more likely to reach weight reductions of at least 10%, 15%, 20% and 25%; the abstract gives no percentages for these.

    Tested in humans under randomised, controlled conditions.

    • The trial was open-label: participants and investigators knew which drug each person received.
    • Semaglutide was given at each participant's maximum tolerated dose, 1.7 mg or 2.4 mg. There was no placebo arm.
    • The figures come from the published abstract only. The full text was not read for this page.
    • The trial was funded by Eli Lilly, the developer.
    • The results describe Lilly's product given under trial conditions. They do not describe compounded tirzepatide or any product sold for research use.
    • The abstract names no estimand, states no difference between the groups in percentage points, and gives no discontinuation rate for adverse events.

    PMID 40353578

  • Human randomised trialSupportive / High confidence

    In a 40-week trial of 478 adults with type 2 diabetes, HbA1c fell more with tirzepatide used on its own than with placebo.

    SURPASS-1, a double-blind phase 3 trial at 52 centres in India, Japan, Mexico and the USA, randomised 478 adults with type 2 diabetes to tirzepatide 5 mg (121), 10 mg (121) or 15 mg (121), or to placebo (115), for 40 weeks. At baseline, mean HbA1c was 7.9%, mean age 54.1 years, mean diabetes duration 4.7 years and mean BMI 31.9. At 40 weeks, mean HbA1c had fallen by 1.87, 1.89 and 2.07 percentage points in the three tirzepatide arms, against a rise of 0.04 percentage points with placebo, estimated differences of -1.91, -1.93 and -2.11 percentage points. Participants had type 2 diabetes inadequately controlled by diet and exercise alone and had not used injectable diabetes therapy.

    Tested in humans under randomised, controlled conditions.

    • The figures come from the published abstract only. The full text was not read for this page.
    • The trial was funded by Eli Lilly, the developer.
    • The results describe Lilly's product given under trial conditions. They do not describe compounded tirzepatide or any product sold for research use.
    • The abstract names no estimand.
    • The abstract gives a weight-loss range for tirzepatide, but no placebo weight figure was retrieved, so no weight figure is given here.

    PMID 34186022

  • Human randomised trialSupportive / High confidence

    In a 40-week open-label trial of 1879 people with type 2 diabetes taking metformin, HbA1c fell more with each dose of tirzepatide than with semaglutide 1 mg.

    SURPASS-2 randomised 1879 patients with type 2 diabetes in a 1:1:1:1 ratio to tirzepatide 5 mg, 10 mg or 15 mg, or semaglutide 1 mg, for 40 weeks. At baseline, mean HbA1c was 8.28%, mean age 56.6 years and mean weight 93.7 kg. At 40 weeks, mean HbA1c had changed by -2.01, -2.24 and -2.30 percentage points with the three tirzepatide doses against -1.86 percentage points with semaglutide. The estimated differences from semaglutide were -0.15 (95% CI -0.28 to -0.03), -0.39 (95% CI -0.51 to -0.26) and -0.45 (95% CI -0.57 to -0.32) percentage points.

    Tested in humans under randomised, controlled conditions.

    • Serious adverse events were reported in 5 to 7% of participants on tirzepatide and 3% on semaglutide.
    • The semaglutide dose was 1 mg, a diabetes dose, not the higher doses used for weight management, so this trial is not a weight comparison with semaglutide's obesity product.
    • The trial was open-label.
    • The figures come from the published abstract only. The full text was not read for this page.
    • The trial was funded by Eli Lilly, the developer.
    • The results describe Lilly's product given under trial conditions. They do not describe compounded tirzepatide or any product sold for research use.
    • The abstract names no estimand and gives the allocation ratio, not the number in each arm.
    • That participants were taking metformin comes from the US Mounjaro label's description of the trial, not from the abstract.
    • The abstract reports greater weight reduction with tirzepatide but gives only the differences between groups, not each group's own change, so no weight figure is given here.

    PMID 34170647fda-label-mounjaro-2026-08

  • Human randomised trialSupportive / High confidence

    In two 52-week trials in adults with moderate to severe obstructive sleep apnoea and obesity, the apnoea-hypopnoea index fell more with tirzepatide than with placebo, both in people not using positive airway pressure and in people using it.

    SURMOUNT-OSA was two double-blind phase 3 trials. Trial 1 enrolled 234 adults not using positive airway pressure (PAP) therapy and trial 2 enrolled 235 who were using it. In each, participants were randomised 1:1 to the maximum tolerated dose of tirzepatide (10 mg or 15 mg) or placebo for 52 weeks. The primary endpoint was the apnoea-hypopnoea index (AHI), the number of apnoeas and hypopnoeas per hour of sleep, which averaged 51.5 events per hour in trial 1 and 49.5 in trial 2 at baseline. Under the treatment-regimen estimand, AHI at week 52 changed in trial 1 by -25.3 events per hour (95% CI -29.3 to -21.2) with tirzepatide against -5.3 (95% CI -9.4 to -1.1) with placebo, a difference of -20.0 (95% CI -25.8 to -14.2). In trial 2 it changed by -29.3 (95% CI -33.2 to -25.4) against -5.5 (95% CI -9.9 to -1.2), a difference of -23.8 (95% CI -29.6 to -17.9).

    Tested in humans under randomised, controlled conditions.

    • These figures were checked against the full text, an author manuscript in PubMed Central.
    • The trials were funded by Eli Lilly, the developer.
    • The results describe Lilly's product given under trial conditions. They do not describe compounded tirzepatide or any product sold for research use.
    • The paper reports a treatment-regimen and an efficacy estimand. Only treatment-regimen results are given here.
    • The number of participants in each arm within each trial is not given here; assignment was 1:1.

    PMID 38912654

  • Human randomised trialSupportive / Moderate confidence

    In a 30-week trial of 99 young people aged 10 to under 18 with type 2 diabetes, HbA1c fell more with tirzepatide than with placebo.

    SURPASS-PEDS, a double-blind phase 3 trial at 39 sites in eight countries, enrolled participants aged 10 to under 18 with youth-onset type 2 diabetes inadequately controlled with metformin, basal insulin or both. It randomised 99, with a mean age of 14.7 years and mean baseline HbA1c of 8.04%, to tirzepatide 5 mg (32), 10 mg (33) or placebo (34). At week 30, HbA1c had fallen by 2.23 percentage points in the two tirzepatide arms pooled, against a rise of 0.05 percentage points with placebo, an estimated difference of -2.28 percentage points (95% CI -2.87 to -1.69). BMI fell by 7.4% with 5 mg and 11.2% with 10 mg, against 0.4% with placebo, at 30 weeks. A 22-week open-label extension followed, in which everyone received tirzepatide.

    Tested in humans under randomised, controlled conditions.

    • The figures come from the published abstract only. The full text was not read for this page.
    • The trial was funded by Eli Lilly, the developer.
    • The results describe Lilly's product given under trial conditions. They do not describe compounded tirzepatide or any product sold for research use.
    • The abstract names no estimand. It analysed everyone who received at least one dose.
    • The HbA1c result is for the 5 mg and 10 mg arms pooled. The abstract gives no HbA1c figure for each arm separately.
    • 99 participants split across three arms, about 33 per arm.
    • The abstract does not say whether the placebo group's 0.4% BMI change was a rise or a fall.

    PMID 40975112

  • Human randomised trialSupportive / High confidence

    In adults with type 2 diabetes and atherosclerotic cardiovascular disease, tirzepatide was not worse than dulaglutide on a composite of cardiovascular death, heart attack or stroke. It was not shown to be better.

    SURPASS-CVOT, a double-blind noninferiority trial, randomised 13,299 people with type 2 diabetes and atherosclerotic cardiovascular disease 1:1 to tirzepatide (up to 15 mg) or dulaglutide 1.5 mg. After 134 were excluded for not meeting the inclusion criteria, the modified intention-to-treat population was 6586 on tirzepatide and 6579 on dulaglutide, with a mean age of 64.1 years, 29.0% women, mean BMI 32.6, mean HbA1c 8.4% and mean diabetes duration 14.7 years. The primary endpoint, a composite of cardiovascular death, myocardial infarction or stroke, occurred in 801 (12.2%) on tirzepatide and 862 (13.1%) on dulaglutide: hazard ratio 0.92 (95.3% CI 0.83 to 1.01). That met the prespecified noninferiority margin of 1.05 for the upper limit of the interval (P = 0.003) but not superiority (P = 0.09). More gastrointestinal adverse events were observed with tirzepatide.

    Tested in humans under randomised, controlled conditions.

    • The comparator was dulaglutide, a drug the paper describes as already shown to reduce cardiovascular events, not placebo. The trial cannot say how tirzepatide compares with no treatment.
    • The paper and the US Mounjaro label analyse different populations. The paper uses the modified intention-to-treat population above and gives P = 0.003 for noninferiority. The label uses all randomised and treated participants, 6,647 per arm, and gives p = 0.007. The paper gives P = 0.09 for superiority; the label states that superiority to dulaglutide was not established.
    • The figures come from the published abstract only. The full text was not read for this page.
    • The trial was funded by Eli Lilly, the developer.
    • The results describe Lilly's product given under trial conditions. They do not describe compounded tirzepatide or any product sold for research use.
    • The abstract names no estimand and states no length of follow-up. The US Mounjaro label gives a median follow-up of 210.1 weeks for its own analysis population.
    • Every participant had type 2 diabetes. The trial says nothing about people with obesity alone.

    PMID 41406444fda-label-mounjaro-2026-08

  • Human randomised trialSupportive / Moderate confidence

    In a trial of 731 people with heart failure with preserved ejection fraction and obesity, cardiovascular death or worsening heart failure occurred less often with tirzepatide than with placebo.

    SUMMIT randomised 731 patients with heart failure, an ejection fraction of at least 50% and a BMI of at least 30, 1:1 to tirzepatide (up to 15 mg, 364 patients) or placebo (367), for at least 52 weeks. Median follow-up was 104 weeks. The composite of adjudicated cardiovascular death or a worsening heart-failure event occurred in 36 patients (9.9%) on tirzepatide and 56 (15.3%) on placebo: hazard ratio 0.62 (95% CI 0.41 to 0.95). Worsening heart-failure events occurred in 29 (8.0%) against 52 (14.2%), hazard ratio 0.54 (95% CI 0.34 to 0.85). Cardiovascular death occurred in 8 (2.2%) against 5 (1.4%), hazard ratio 1.58 (95% CI 0.52 to 4.83). Adverse events, mainly gastrointestinal, led to stopping the trial drug in 23 (6.3%) on tirzepatide and 5 (1.4%) on placebo.

    Tested in humans under randomised, controlled conditions.

    • Heart failure is not an approved indication for tirzepatide in the US or the EU. Neither current US label lists it, and the EU product information refers to this trial's results without listing it as an indication.
    • The benefit in the composite came from fewer worsening heart-failure events. Cardiovascular deaths were numerically more frequent with tirzepatide, 8 against 5, with a wide confidence interval.
    • The figures come from the published abstract only. The full text was not read for this page. The abstract names no estimand.
    • The trial had a second primary endpoint, a score the abstract abbreviates as KCCQ-CSS. It is not described here.
    • The trial was funded by Eli Lilly, the developer.
    • The results describe Lilly's product given under trial conditions. They do not describe compounded tirzepatide or any product sold for research use.

    PMID 39555826fda-label-zepbound-2026-08fda-label-mounjaro-2026-08ema-mounjaro-product-information

Reported and theoretical risks

  • Human RCTmoderate

    Gastrointestinal adverse events, including nausea, diarrhoea and vomiting

    Gastrointestinal events were the most common adverse events in SURMOUNT-1, which described them as mostly mild to moderate and occurring primarily during dose escalation. In SURPASS-1, in adults with type 2 diabetes, during the 40-week trial, nausea occurred in 12 to 18% of participants across the tirzepatide arms against 6% with placebo, diarrhoea in 12 to 14% against 8%, and vomiting in 2 to 6% against 2%. In SURPASS-2, against semaglutide 1 mg, nausea occurred in 17 to 22% against 18%, diarrhoea in 13 to 16% against 12%, and vomiting in 6 to 10% against 8%. In SURMOUNT-1, adverse events of any kind led to stopping treatment in 4.3%, 7.1% and 6.2% of the 5 mg, 10 mg and 15 mg arms against 2.6% with placebo; that figure is higher at 10 mg than at 15 mg, and the abstract does not say how much of it was gastrointestinal. The US Zepbound label pools SURMOUNT-1 and SURMOUNT-2 and reports, as label data rather than a trial paper, gastrointestinal adverse reactions in 56% of each tirzepatide arm against 30% with placebo, and nausea in 25%, 29% and 28% of the 5 mg, 10 mg and 15 mg arms against 8%.

  • Human RCTmoderate

    Hypoglycaemia

    In SURPASS-1, where tirzepatide was used on its own in people whose diabetes diet and exercise had not controlled, no clinically significant (below 54 mg/dL, or 3 mmol/L) or severe hypoglycaemia was reported with tirzepatide. In SURPASS-2, in people with type 2 diabetes, hypoglycaemia below 54 mg/dL was reported in 0.6%, 0.2% and 1.7% of the 5 mg, 10 mg and 15 mg arms, against 0.4% with semaglutide 1 mg. In the weight-management trial in people with type 2 diabetes, the US Zepbound label reports hypoglycaemia below 54 mg/dL in 4.2% on tirzepatide against 1.3% on placebo. The US Mounjaro label carries a warning headed 'Hypoglycemia with Concomitant Use of Insulin Secretagogues or Insulin'.

  • Human RCTserious

    Acute pancreatitis

    In SURMOUNT-OSA, a 52-week trial in adults with obstructive sleep apnoea and obesity, the full text reports adjudication-confirmed acute pancreatitis in 2 of 119 participants (1.7%) on tirzepatide in trial 2, the trial of participants using positive airway pressure, against 0 of 114 on placebo; trial 1 had none in either group. The US Zepbound label gives the larger pooled figures, as label data: in the two weight-reduction trials, 0.2% on tirzepatide had adjudication-confirmed acute pancreatitis against 0.2% on placebo (0.14 and 0.15 patients per 100 years of exposure); in the two sleep apnoea trials, 0.84 patients per 100 years on tirzepatide against 0 on placebo. Numbers this small cannot settle whether the risk is raised.

Regulatory status

Status differs by country and changes over time. Each entry is dated and sourced.

  • USFDAapproved

    Zepbound. Its current US label, revised 08/2026, lists two indications, each in combination with a reduced-calorie diet and increased physical activity: to reduce excess body weight and maintain weight reduction long term in adults with obesity, or with overweight and at least one weight-related comorbid condition; and to treat moderate to severe obstructive sleep apnoea in adults with obesity. It carries a boxed warning that tirzepatide causes thyroid C-cell tumours in rats, and that it is unknown whether it causes them, including medullary thyroid carcinoma, in humans.

    As of 3 October 2026. Source

  • USFDAapproved

    Mounjaro. Its current US label, revised 08/2026, lists two indications: alongside diet and exercise, to improve glycaemic control in adults and children aged 10 and older with type 2 diabetes; and to reduce the risk of major adverse cardiovascular events (cardiovascular death, non-fatal myocardial infarction or non-fatal stroke) in adults with type 2 diabetes at high risk of them. It carries the same boxed warning on thyroid C-cell tumours in rats, and contraindicates use in people with a personal or family history of medullary thyroid carcinoma or with multiple endocrine neoplasia syndrome type 2 (MEN 2).

    As of 3 October 2026. Source

  • EUEMAapproved

    EMA's register of the medicines it has assessed, in the copy generated on 2 October 2026, has one tirzepatide entry: Mounjaro, authorised, with marketing authorisation on 15 September 2022, held by Eli Lilly Nederland B.V. Its indications are type 2 diabetes from age 10 and weight management. Its indication text points readers to section 5.1 of the product information for trial results in obstructive sleep apnoea and heart failure with preserved ejection fraction, and lists neither as an indication.

    As of 2 October 2026. Source

Related peptides

  • RetatrutideRetatrutide is an investigational triple receptor agonist with published phase 3 trials

Sources

  1. 1. Jastreboff AM et al. Tirzepatide Once Weekly for the Treatment of Obesity.. The New England Journal of Medicine. 2022. PubMed 35658024
  2. 2. Garvey WT et al. Tirzepatide once weekly for the treatment of obesity in people with type 2 diabetes (SURMOUNT-2): a double-blind, randomised, multicentre, placebo-controlled, phase 3 trial.. The Lancet. 2023. PubMed 37385275
  3. 3. Aronne LJ et al. Continued Treatment With Tirzepatide for Maintenance of Weight Reduction in Adults With Obesity: The SURMOUNT-4 Randomized Clinical Trial.. JAMA. 2024. PubMed 38078870
  4. 4. Aronne LJ et al. Tirzepatide as Compared with Semaglutide for the Treatment of Obesity.. The New England Journal of Medicine. 2025. PubMed 40353578
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