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Side-by-side comparison

Tirzepatide vs Retatrutide

Both molecules come from Eli Lilly. Tirzepatide is an approved medicine. Retatrutide is still in clinical trials and is not approved by any regulator. Retatrutide adds a third target, the glucagon receptor, to the two that tirzepatide acts on.

Last verified 2026-09-29 · how we verify

In plain English

The real difference

  • Tirzepatide acts on the GIP receptor and GLP-1 receptor. Retatrutide acts on the GIP receptor, GLP-1 receptor and glucagon receptor.[src][src]
  • Tirzepatide is an approved medicine.[src]
  • Retatrutide is not approved by any regulator yet; the strongest evidence so far is from phase 3 trials.[src]
  • Both come from the same company, Eli Lilly.
  • Tirzepatide is taken as a once-weekly injection; retatrutide as a once-weekly injection (in clinical trials).
  • Half-life (how long until half the drug has left the blood): Tirzepatide, about 5 days (5 to 6 days in adults with obesity); retatrutide, about 6 days (phase 1b study in type 2 diabetes).[src][src]
  • Our sources include no head-to-head trial between them. Their results come from different trials, with different people, durations and methods, so the numbers below are not directly comparable.

Which one suits a person is a decision for them and their clinician.

Tirzepatide and Retatrutide, side by side

Tirzepatide compared with Retatrutide
TirzepatideEli LillyRetatrutideEli Lilly
The basics
MoleculeTirzepatideRetatrutide
Brand namesMounjaro, ZepboundNone: not an approved medicine
MakerSame for both
Acts onThe hormone receptors the drug switches onGIP receptor, GLP-1 receptorGIP receptor, GLP-1 receptor, Glucagon receptor
Approved to treat
  • Mounjaro: Type 2 diabetes (adults and children 10 and older); reducing major cardiovascular events in adults with type 2 diabetes at high risk (US label)
  • Zepbound: Chronic weight management in adults with obesity, or overweight with a weight-related condition; moderate-to-severe obstructive sleep apnea in adults with obesity (US label)
None: not an approved medicine
How it is takenSubcutaneous injection, given once a week, supplied as prefilled pens or vialsInvestigational. In clinical trials it is given by subcutaneous injection once a week. It has no approved route because it is not approved anywhere. Lilly's May 2026 release described it as legally available only to participants in Lilly's clinical trials. Since June 2026 Lilly has also listed a pre-approval, single-patient expanded-access programme, requested by a treating physician, for a narrow group of adults with severe obesity who cannot join a trial.
Half-lifeHow long until half the drug has left the bloodAbout 5 days (5 to 6 days in adults with obesity)[src]About 6 days (phase 1b study in type 2 diabetes)[src]
Evidence and safety
Evidence level
Approved. Approved by a major regulator after large trials.
Phase 3. Large trials comparing it with placebo or other drugs.
Approvals and filings
  • FDA approval for type 2 diabetes. Approved on 13 May 2022 as Mounjaro, to improve blood sugar control in adults with type 2 diabetes as an addition to diet and exercise.[src]
  • FDA approval for weight management. Approved on 8 November 2023 as Zepbound for chronic weight management in adults with obesity, or overweight with a weight-related condition.[src]
  • FDA approval for sleep apnea. Zepbound approved on 20 December 2024 for moderate-to-severe obstructive sleep apnea in adults with obesity.[src]
  • EU authorisation. Marketing authorisation for Mounjaro granted on 15 September 2022; the EU indications cover type 2 diabetes (adults and children 10 and older) and weight management in adults. Sleep apnea is not a separate EU indication.[src]
  • Regulatory status. Not approved by any regulator as of 2026-09-29. Lilly says it plans to submit a Biologics License Application to the US FDA in Q1 2027. Lilly describes it as an investigational molecule that cannot be legally sold or marketed for human use.[src]
Key trial resultsTrials test the molecule, not a brand; each result names its population
  • SURMOUNT-1 weight change at 72 weeks. -20.9% at the highest of three maintenance doses versus -3.1% with placebo (2,539 adults with obesity, or overweight with a weight-related condition, and without diabetes).[src]
  • SURMOUNT-5 versus semaglutide. -20.2% with tirzepatide versus -13.7% with semaglutide at 72 weeks (751 adults, open-label).[src]
  • TRIUMPH-1 (obesity, 80 weeks). Highest dose: mean weight change -28.3% versus -2.2% with placebo (efficacy estimand); -25.0% versus -3.9% (treatment-regimen estimand). 2,339 randomised adults without diabetes. Company topline result, not yet peer-reviewed.[src]
  • TRIUMPH-1 extension (104 weeks). In a pre-specified extension of 532 participants with baseline BMI of 35 or more who completed the main study and tolerated their dose, mean weight change was -30.3% at 104 weeks in the group that continued the highest dose (a selected subgroup).[src]
  • TRIUMPH-2 and TRIUMPH-3 (80 weeks). Type 2 diabetes with obesity (n=1,152): up to -20.8% versus -4.0% placebo. Severe obesity with cardiovascular disease (n=1,949): up to -22.6% versus -3.2% placebo. Efficacy estimand, company topline results.[src]
  • TRANSCEND-T2D-1 (peer-reviewed phase 3). 537 adults with type 2 diabetes, 40 weeks: HbA1c change -1.69% to -1.94% versus -0.81% with placebo; weight change -11.5% to -15.3% versus -2.6% (treatment-regimen estimand).[src]
Known safety signals
  • Boxed warning: in rats, tirzepatide caused thyroid C-cell tumours at clinically relevant exposures. It is unknown whether it causes these tumours, including medullary thyroid carcinoma, in humans. It is contraindicated in people with a personal or family history of medullary thyroid carcinoma or with Multiple Endocrine Neoplasia syndrome type 2.[src]
  • In SURPASS-2, the most common adverse events with tirzepatide were gastrointestinal and mostly mild to moderate: nausea in 17 to 22%, diarrhoea in 13 to 16% and vomiting in 6 to 10% of the three tirzepatide groups. Serious adverse events were reported in 5 to 7% of tirzepatide patients and 3% of semaglutide patients.[src]
  • US labels list nausea, diarrhoea, vomiting, constipation, abdominal pain and dyspepsia among the most common adverse reactions (5% or more of patients), and warn of serious gastrointestinal reactions (not recommended in severe gastroparesis), acute kidney injury from dehydration, acute gallbladder disease and acute pancreatitis.[src]
  • The label states that the risk of hypoglycaemia, including severe hypoglycaemia, is increased when tirzepatide is used with insulin or an insulin secretagogue such as a sulfonylurea.[src]
  • Because it delays gastric emptying, tirzepatide can affect the absorption of oral medicines, and there are rare postmarketing reports of pulmonary aspiration in people taking GLP-1 receptor agonists who had elective procedures under general anaesthesia or deep sedation.[src]
  • Other label warnings include serious hypersensitivity reactions (anaphylaxis, angioedema) reported after marketing, monitoring for diabetic retinopathy complications in people with type 2 diabetes and a history of retinopathy, and possible fetal harm in pregnancy.[src]
  • In TRIUMPH-1 the most common adverse events were gastrointestinal. At the highest dose versus placebo: nausea 42.4% vs 14.8%, diarrhoea 32.0% vs 13.5%, vomiting 25.3% vs 4.8%, constipation 26.1% vs 10.9%. Dysesthesia (abnormal skin sensations such as tingling or altered touch) was reported in 12.5% vs 0.9%, and urinary tract infections in 8.4% vs 5.3%. Discontinuation due to adverse events was 11.3% at the highest dose versus 4.9% with placebo. Retatrutide has no approved label, so there is no boxed warning or official safety statement yet.[src]
  • In TRIUMPH-4 (knee osteoarthritis), dysesthesia (abnormal skin sensations such as tingling or altered touch) was reported in 8.8% and 20.9% of people on the two retatrutide doses versus 0.7% with placebo. Lilly described these events as generally mild and said they rarely led to stopping treatment. In TRIUMPH-4 (knee osteoarthritis), discontinuation due to adverse events was 18.2% at the highest dose versus 4.0% with placebo; Lilly said these rates correlated with baseline BMI and included stopping for perceived excessive weight loss.[src]
  • The phase 2 obesity trial reported dose-dependent increases in heart rate that peaked at 24 weeks and declined thereafter, and gastrointestinal events that were dose-related and mostly mild to moderate.[src]
  • In a warning letter dated 2026-03-31 to a firm whose products included retatrutide, FDA stated that the products were unapproved new drugs. It said that, despite 'Research Use Only' and 'not intended for human consumption' labelling, evidence from the firm's website showed the products were intended as drugs, and noted that injectable products bypass some of the body's key defences against toxins and microorganisms.[src]
  • Australia's TGA warns that many peptide products supplied in Australia are unapproved, have not been assessed by the TGA for safety, quality or effectiveness, may not meet required standards and may be incorrectly labelled. This release is about unapproved peptides in general and does not name retatrutide.[src]
  • A 2026 case report described a man with type 1 diabetes who developed ketosis and acute kidney injury after using an online-purchased product marketed as retatrutide. The author states that causation cannot be established: stool culture also grew Shigella, and he had omitted insulin while unwell.[src]
Legal status
United States
Approved

FDA-approved as Mounjaro (type 2 diabetes) and Zepbound (weight management, sleep apnea); shortage over since December 2024[src]

Full detail →
Prohibited

Not approved; FDA says retatrutide cannot be compounded and has warned sellers, so lawful access is limited to trials and expanded access[src]

Full detail →
United Kingdom
Approved

Licensed in the UK as Mounjaro for type 2 diabetes and for weight management; NHS access is being phased in[src]

Full detail →
Prohibited

Not authorised in the UK; the MHRA says selling it is illegal and has raided sites making and supplying it[src]

Full detail →
European Union
Approved

Authorised EU-wide as Mounjaro for type 2 diabetes and for weight management in adults[src]

Full detail →
Not approved

Investigational; no EU marketing authorisation and no application under evaluation[src]

Full detail →
Australia
Approved

Approved as Mounjaro for type 2 diabetes (Dec 2022) and weight management (Sep 2024). Not PBS-listed: the sponsor is not proceeding for now. Compounding barred since Oct 2024.[src]

Full detail →
Prohibited

Not approved by the TGA or any comparable regulator. The TGA names retatrutide in peptide warnings and seizures, and a product sold as retatrutide contained semaglutide instead.[src]

Full detail →
Canada
Approved

Approved as Mounjaro (type 2 diabetes) and Zepbound (weight management, sleep apnea); no generic submissions[src]

Full detail →
Prohibited

Not authorised; Health Canada named retatrutide among unauthorised injectable drugs it has seized (April 2026)[src]

Full detail →

Trial results come from separate studies unless a row says it is a head-to-head trial. Populations, durations and methods differ, so compare numbers across columns with care.

Go deeper

Molecule

Tirzepatide explained →Watch the 3D body journey →

Molecule

Retatrutide explained →Watch the 3D body journey →

Educational information only. Not medical advice, not a recommendation to use any substance, and not an offer to supply. Talk to a licensed clinician about your own care.

Sources (69)

  1. 01Tirzepatide Once Weekly for the Treatment of Obesity (SURMOUNT-1)New England Journal of Medicine · 2022-07-21 · accessed 2026-09-29
  2. 02Tirzepatide versus Semaglutide Once Weekly in Patients with Type 2 Diabetes (SURPASS-2)New England Journal of Medicine · 2021-08-05 · accessed 2026-09-29
  3. 03Tirzepatide as Compared with Semaglutide for the Treatment of Obesity (SURMOUNT-5)New England Journal of Medicine · 2025-07-03 · accessed 2026-09-29
  4. 04Tirzepatide for the Treatment of Obstructive Sleep Apnea and Obesity (SURMOUNT-OSA)New England Journal of Medicine · 2024-10-03 · accessed 2026-09-29
  5. 05Tirzepatide for Heart Failure with Preserved Ejection Fraction and Obesity (SUMMIT)New England Journal of Medicine · 2025-01-30 · accessed 2026-09-29
  6. 06Cardiovascular Outcomes with Tirzepatide versus Dulaglutide in Type 2 Diabetes (SURPASS-CVOT)New England Journal of Medicine · 2025-12-18 · accessed 2026-09-29
  7. 07MOUNJARO (tirzepatide) injection, prescribing informationU.S. National Library of Medicine (DailyMed), FDA-approved label · 2026-09 · accessed 2026-09-29
  8. 08ZEPBOUND (tirzepatide) injection, prescribing informationU.S. National Library of Medicine (DailyMed), FDA-approved label · 2026-09 · accessed 2026-09-29
  9. 09Drug Trials Snapshots: MOUNJAROU.S. Food and Drug Administration · 2023-06-13 · accessed 2026-09-29
  10. 10FDA Approves New Medication for Chronic Weight ManagementU.S. Food and Drug Administration · 2023-11-08 · accessed 2026-09-29
  11. 11FDA Approves First Medication for Obstructive Sleep ApneaU.S. Food and Drug Administration · 2024-12-20 · accessed 2026-09-29
  12. 12Mounjaro (tirzepatide): European public assessment reportEuropean Medicines Agency · 2022-09-15 · accessed 2026-09-29
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  14. 14ZEPBOUND (tirzepatide) injection prescribing informationU.S. Food and Drug Administration · 2026-09 · accessed 2026-09-29
  15. 15FDA clarifies policies for compounders as national GLP-1 supply begins to stabilizeU.S. Food and Drug Administration · 2026-04-01 · accessed 2026-09-29
  16. 16List of Bulk Drug Substances for Which There Is a Clinical Need Under Section 503B (proposal not to include semaglutide, tirzepatide, liraglutide)Federal Register (FDA) · 2026-05-01 · accessed 2026-09-29
  17. 17FDA's Concerns with Unapproved GLP-1 Drugs Used for Weight LossU.S. Food and Drug Administration · 2026-09-01 · accessed 2026-09-29
  18. 18MHRA authorises diabetes drug Mounjaro (tirzepatide) for weight management and weight lossMedicines and Healthcare products Regulatory Agency (MHRA) · 2023-11-08 · accessed 2026-09-29
  19. 19Tirzepatide for managing overweight and obesity (TA1026)National Institute for Health and Care Excellence (NICE) · 2024-12-23 · accessed 2026-09-29
  20. 20Mounjaro (tirzepatide) price increase: Drug Tariff redeterminationNHS Business Services Authority (NHSBSA) · 2025-09 · accessed 2026-09-29
  21. 21Fake Mounjaro (tirzepatide) KwikPen 15mg pre-filled pensMedicines and Healthcare products Regulatory Agency (MHRA) · 2026-02-24 · accessed 2026-09-29
  22. 22New diabetes and obesity medicines: an AIFA guideItalian Medicines Agency (AIFA) · 2026-05-18 · accessed 2026-09-29
  23. 23Obesite: prise en charge de Wegovy et Mounjaro a partir du 15 juin 2026, sous conditionsVidal · 2026-05-28 · accessed 2026-09-29
  24. 24Arzneimittel-Richtlinie Anlage II: Lifestyle-Arzneimittel (Stand 20. August 2025)Gemeinsamer Bundesausschuss (G-BA) · 2025-08-20 · accessed 2026-09-29
  25. 25MOUNJARO tirzepatide solution for injection pre-filled pen (ARTG 379330)Therapeutic Goods Administration (TGA) · 2022-12 · accessed 2026-09-29
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  30. 30Prescription medicines under evaluation: Mounjaro (tirzepatide), cardiovascular risk reduction (accepted December 2025)Therapeutic Goods Administration (TGA) · 2025-12 · accessed 2026-09-29
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  36. 36Unauthorized injectable peptide drugs seized and sold by Canada Peptide may pose serious health risksHealth Canada · 2025-08-01 · accessed 2026-09-29
  37. 37Thinking about buying GLP-1 drugs like Ozempic or Mounjaro? Beware of fake or unauthorized productsHealth Canada · 2026-01-21 · accessed 2026-09-29
  38. 38Triple-Hormone-Receptor Agonist Retatrutide for Obesity - A Phase 2 TrialNew England Journal of Medicine (PubMed) · 2023-08-10 · accessed 2026-09-29
  39. 39Retatrutide, a GIP, GLP-1 and glucagon receptor agonist, for people with type 2 diabetes: a randomised, double-blind, placebo and active-controlled, parallel-group, phase 2 trial conducted in the USAThe Lancet (PubMed) · 2023-08-12 · accessed 2026-09-29
  40. 40Efficacy and safety of retatrutide, a GIP, GLP-1, and glucagon receptor agonist, in people with type 2 diabetes and inadequate glycaemic control with diet and exercise (TRANSCEND-T2D-1): a double-blind, randomised, phase 3 trialThe Lancet (PubMed) · 2026-06-13 · accessed 2026-09-29
  41. 41Lilly's triple agonist, retatrutide, delivered powerful weight loss in pivotal Phase 3 obesity trial (TRIUMPH-1 topline)Eli Lilly and Company (PR Newswire) · 2026-05-21 · accessed 2026-09-29
  42. 42Lilly's triple agonist, retatrutide, successful in two additional Phase 3 obesity trials (TRIUMPH-2 and TRIUMPH-3 topline)Eli Lilly and Company (PR Newswire) · 2026-07-23 · accessed 2026-09-29
  43. 43Lilly's triple agonist, retatrutide, delivered weight loss of up to an average of 71.2 lbs along with substantial relief from osteoarthritis pain in first successful Phase 3 trial (TRIUMPH-4 topline)Eli Lilly and Company (PR Newswire) · 2025-12-11 · accessed 2026-09-29
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  64. 64TGA flexes its muscle against illegal peptides and steroidsTherapeutic Goods Administration (TGA) · 2026-08-17 · accessed 2026-09-29
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