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Tirzepatide

Dual GIP and GLP-1 receptor agonist

Status

Approved

Approved by the FDA (Mounjaro 2022, Zepbound 2023) and EMA (2022) for type 2 diabetes, weight management and, in the US, obesity-related sleep apnea, with a US cardiovascular-risk indication added in August 2026; the FDA confirmed the shortage resolved on December 19, 2024, and enforcement discretion for compounded copies ended on February 18, 2025 (503A) and March 19, 2025 (503B).

Evidence

Strong

Multiple large phase 3 programs (SURPASS, SURMOUNT) plus a cardiovascular outcomes trial (SURPASS-CVOT) support its approved uses.

Tirzepatide is a once-weekly injected peptide that activates both GIP and GLP-1 receptors. It is approved for type 2 diabetes, chronic weight management and obesity-related sleep apnea, and in the US to lower cardiovascular risk in high-risk type 2 diabetes.

Structure

39 residues
  1. aK20C20 fatty diacid (eicosanedioic acid) via γGlu-2xOEG linker (albumin binding)

Point at a bead, or focus the chain and use the arrow keys, to name it. Pick a chemistry to highlight it.

Sequence as text
H-Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-D-K-I-A-Q-K-A-F-V-Q-W-L-I-A-G-G-P-S-S-G-A-P-P-P-S-NH2

What it is used for

  • Type 2 diabetes in adults and children 10 and older, glycemic control (approved)
  • Chronic weight management in adults (approved)
  • Moderate to severe obstructive sleep apnea with obesity (approved)
  • Reducing major cardiovascular events in high-risk type 2 diabetes (approved)
  • Heart failure with preserved ejection fraction and obesity (studied)

How it works

Tirzepatide is built on the sequence of GIP, a gut hormone, but also activates the GLP-1 receptor. Together these actions increase glucose-dependent insulin release, lower glucagon, slow stomach emptying and reduce appetite and food intake. Aib residues at positions 2 and 13 protect it from breakdown by DPP-4, and a C20 fatty diacid on Lys20 binds albumin, giving a half-life of about five days that allows weekly dosing.

How strong the evidence is

StrongSeveral large randomised controlled trials in people.

SURMOUNT-1 (2,539 adults with obesity, no diabetes) found mean weight loss of 15.0% to 20.9% at 72 weeks across 5 to 15 mg versus 3.1% with placebo. SURMOUNT-5 showed greater weight loss than semaglutide 2.4 mg (20.2% vs 13.7%). In type 2 diabetes, SURPASS-2 found larger HbA1c reductions than semaglutide 1 mg, and SURPASS-CVOT (13,165 patients) showed non-inferiority to dulaglutide for major cardiovascular events (12.2% vs 13.1%). SURMOUNT-OSA cut the apnea-hypopnea index by about 20 events per hour more than placebo. SUMMIT studied heart failure with preserved ejection fraction.

Risks and side effects

  • Nausea, diarrhea, vomiting and constipation, mostly during dose escalation
  • Boxed warning: thyroid C-cell tumors in rats; contraindicated with a personal or family history of medullary thyroid cancer or MEN 2
  • Acute pancreatitis, gallbladder disease and acute kidney injury from dehydration
  • Hypoglycemia with insulin or insulin secretagogues, and diabetic retinopathy complications in people with prior retinopathy
  • Risk of pulmonary aspiration during general anesthesia or deep sedation

Label dosing

Label: start at 2.5 mg once weekly for 4 weeks, then increase in 2.5 mg steps at least 4 weeks apart to a maintenance dose of 5 to 15 mg weekly (maximum 15 mg).

Summarised from the official prescribing information. Not a recommendation: dosing is decided with a prescriber.

Regulatory status

RegionYearApproved for
USFDA2022Type 2 diabetes (adults; children 10 and older from December 2025)
USFDA2023Chronic weight management in adults with obesity or overweight with a weight-related condition
USFDA2024Moderate to severe obstructive sleep apnea in adults with obesity
USFDA2026Reducing major cardiovascular events in adults with type 2 diabetes at high cardiovascular risk
EUEMA2022Type 2 diabetes (including children 10 and older) and, by later extension, weight management

Status by country

JurisdictionStatusSource
USUnited StatesAuthorised medicineSource 3
EUEuropean UnionAuthorised medicineSource 12
UKUnited KingdomAuthorised medicineSource 14
AUAustraliaAuthorised medicineSource 15
CACanadaAuthorised medicineSource 16
Whether a medicine containing it is authorised, checked in each regulator’s records on Oct 1, 2026.

Status of every peptide by country

Trials of Tirzepatide to watch

  1. Phase 3Active, not recruiting

    SURMOUNT-ADOLESCENTS(opens the source in a new tab)

    A Study of Tirzepatide (LY3298176) Once Weekly in Adolescent Participants Who Have Obesity or Overweight With Weight-Related Comorbidities

    Primary completion Jun 2, 2026160 participantsSponsor: Eli Lilly and CompanyNCT06075667

  2. Phase 3Active, not recruiting

    SURPASS-T1D-1(opens the source in a new tab)

    A Study of Tirzepatide (LY3298176) Compared With Placebo in Adults With Type 1 Diabetes and Obesity or Overweight

    Primary completion expected November 2026905 participantsSponsor: Eli Lilly and CompanyNCT06914895

  3. Phase 3Active, not recruiting

    TRIUMPH-5(opens the source in a new tab)

    A Study of Retatrutide (LY3437943) Compared to Tirzepatide (LY3298176) in Adults Who Have Obesity

    Primary completion expected November 2026800 participantsSponsor: Eli Lilly and CompanyNCT06662383

  4. Phase 2Active, not recruiting

    LOCITT(opens the source in a new tab)

    The Long COVID Treatment Trial

    Primary completion expected December 20261,000 participantsSponsor: Scripps Translational Science InstituteNCT07128082

  5. Phase 2Recruiting

    TAB(opens the source in a new tab)

    Evaluation of Tirzepatide as an Adjunct to Buprenorphine for the Treatment of Opioid Use Disorder

    Primary completion expected Sep 30, 2027310 participantsSponsor: T. John Winhusen, PhDNCT06651177

  6. Phase 3Active, not recruiting

    SURMOUNT-MMO(opens the source in a new tab)

    A Study of Tirzepatide (LY3298176) on the Reduction on Morbidity and Mortality in Adults With Obesity

    Primary completion expected October 202715,374 participantsSponsor: Eli Lilly and CompanyNCT05556512

  7. Phase 3Completed

    TOGETHER-PsO(opens the source in a new tab)

    Ixekizumab Concomitantly Administered With Tirzepatide in Adults With Moderate-to-Severe Plaque Psoriasis and Obesity or Overweight

    Primary completion Jan 8, 2026281 participantsSponsor: Eli Lilly and CompanyNCT06588283

  8. Phase 3Completed

    CagriSema vs tirzepatide in obesity(opens the source in a new tab)

    A Research Study to See How Well CagriSema Compared to Tirzepatide Helps People With Obesity Lose Weight

    Primary completion Dec 8, 2025809 participantsSponsor: Novo Nordisk A/SNCT06131437

All trials to watch

Timeline

  1. 2027

    1. SURMOUNT-MMO
    2. TAB

  2. 2026

    1. LOCITT
    2. TRIUMPH-5
    3. SURPASS-T1D-1
    4. Trial resultEloralintide with tirzepatide reduces weight in phase 2b trial
    5. RegulatoryFDA says compounded GLP-1s with added vitamins are still copies of approved drugs
    6. RegulatoryWADA keeps GLP-1 drugs off its 2027 Prohibited List and continues monitoring
    7. ResearchESC heart failure guidelines back semaglutide or tirzepatide in HFpEF with obesity
    8. ApprovalFDA approves Mounjaro to lower heart attack, stroke and CV death risk in type 2 diabetes
    9. RegulatoryAppeals court upholds FDA decisions ending the tirzepatide and semaglutide shortages
    10. RegulatoryFDA warning letters reject 'research use only' labels on online GLP-1 peptide sales
Show 24 earlier events

  1. 2026

    1. ResearchBMJ review of 262 trials: semaglutide the only obesity drug linked to lower mortality
    2. MarketMedicare GLP-1 Bridge starts, covering obesity drugs for a $50 monthly copay
    3. RegulatoryEMA declines new heart-risk indication for Mounjaro but adds trial data to label
    4. ResearchAmerican College of Physicians names semaglutide and tirzepatide first-line obesity drugs
    5. SURMOUNT-ADOLESCENTS
    6. RegulatoryFDA proposes barring outsourcing facilities from compounding semaglutide and tirzepatide
    7. Trial resultCagriSema misses non-inferiority goal against tirzepatide in REDEFINE 4
    8. SafetyUK regulator strengthens GLP-1 warnings on severe, necrotising and fatal pancreatitis
    9. SafetyFDA asks makers to drop suicidal-thoughts warning from GLP-1 weight-loss drug labels
    10. TOGETHER-PsO
    11. Approved, US (FDA)Reducing major cardiovascular events in adults with type 2 diabetes at high cardiovascular risk

  2. 2025

    1. CagriSema vs tirzepatide in obesity
    2. RegulatoryWHO issues first guideline on GLP-1 medicines for obesity, with conditional backing
    3. RegulatoryUK regulator raids first illegal weight-loss pen factory, seizing retatrutide pens
    4. RegulatoryWHO adds semaglutide, tirzepatide and other GLP-1 drugs to its essential medicines list
    5. Trial resultSURPASS-CVOT: tirzepatide matches dulaglutide on heart outcomes in type 2 diabetes
    6. MarketNovo Nordisk launches NovoCare Pharmacy selling Wegovy at $499 a month to cash payers

  3. 2024

    1. ApprovalFDA approves Zepbound as first drug for obstructive sleep apnea in adults with obesity
    2. RegulatoryFDA confirms tirzepatide shortage is over, starting wind-down of compounded copies
    3. Trial resultSURMOUNT-5: tirzepatide beats semaglutide on weight loss in head-to-head trial
    4. Approved, US (FDA)Moderate to severe obstructive sleep apnea in adults with obesity

  4. 2023

    1. Approved, US (FDA)Chronic weight management in adults with obesity or overweight with a weight-related condition

  5. 2022

    1. Approved, US (FDA)Type 2 diabetes (adults; children 10 and older from December 2025)
    2. Approved, EU (EMA)Type 2 diabetes (including children 10 and older) and, by later extension, weight management

Articles about Tirzepatide

Sources

  1. 01Mounjaro (tirzepatide) injection: prescribing information(opens the source in a new tab) DailyMed, U.S. National Library of Medicine, 2026
  2. 02Zepbound (tirzepatide) injection: prescribing information(opens the source in a new tab) DailyMed, U.S. National Library of Medicine, 2026
  3. 03Drugs@FDA: Mounjaro (NDA 215866) approval history(opens the source in a new tab) U.S. Food and Drug Administration, 2026
  4. 04Tirzepatide (D11360): sequence and structure entry(opens the source in a new tab) KEGG DRUG
  5. 05Tirzepatide (CID 166567236)(opens the source in a new tab) PubChem, U.S. National Library of Medicine
  6. 06Tirzepatide Once Weekly for the Treatment of Obesity (SURMOUNT-1)(opens the source in a new tab) New England Journal of Medicine, 2022
  7. 07Tirzepatide as Compared with Semaglutide for the Treatment of Obesity (SURMOUNT-5)(opens the source in a new tab) New England Journal of Medicine, 2025
  8. 08Tirzepatide versus Semaglutide Once Weekly in Patients with Type 2 Diabetes (SURPASS-2)(opens the source in a new tab) New England Journal of Medicine, 2021
  9. 09Cardiovascular Outcomes with Tirzepatide versus Dulaglutide in Type 2 Diabetes (SURPASS-CVOT)(opens the source in a new tab) New England Journal of Medicine, 2025
  10. 10Tirzepatide for the Treatment of Obstructive Sleep Apnea and Obesity (SURMOUNT-OSA)(opens the source in a new tab) New England Journal of Medicine, 2024
  11. 11Tirzepatide for Heart Failure with Preserved Ejection Fraction and Obesity (SUMMIT)(opens the source in a new tab) New England Journal of Medicine, 2025
  12. 12Mounjaro: EPAR (European public assessment report)(opens the source in a new tab) European Medicines Agency, 2026
  13. 13FDA clarifies policies for compounders as national GLP-1 supply begins to stabilize(opens the source in a new tab) U.S. Food and Drug Administration, 2025
  14. 14Mounjaro KwikPen solution for injection in pre-filled pen: Summary of Product Characteristics(opens the source in a new tab) electronic medicines compendium (emc), 2026
  15. 15MOUNJARO tirzepatide 5 mg/0.5 mL solution for injection pre-filled pen (379330)(opens the source in a new tab) Therapeutic Goods Administration
  16. 16Drug Product Database: Mounjaro (DIN 02541041)(opens the source in a new tab) Health Canada, 2026
  1. In clinical trialsAmycretinUnimolecular GLP-1 and amylin receptor agonistNo single sequence68 WADA banned
  2. Not approvedAOD-9604Modified growth hormone fragment (research peptide)16 WADA banned
  3. In clinical trialsCagrilintideLong-acting amylin analog (amylin and calcitonin receptor agonist)37 WADA banned
  4. ApprovedDulaglutideGLP-1 receptor agonist (Fc fusion protein)31
  5. ApprovedExenatideGLP-1 receptor agonist39

Educational information, not medical advice. Talk to a licensed clinician before starting, stopping or changing any medicine.