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Monograph in Incretin & amylin agonists

Tirzepatide

The first approved dual GIP and GLP-1 receptor agonist — and, in the only head-to-head obesity trial, more effective for weight than semaglutide.

Also called LY3298176 · Mounjaro · Zepbound

A

Best evidence: Approved / regulatory-grade

FDA-approved for type 2 diabetes (Mounjaro) and for chronic weight management and obstructive sleep apnea with obesity (Zepbound).

FDA-approved — Mounjaro (2022), Zepbound (2023)

Residue Editorial Team · updated

What is Tirzepatide?

Tirzepatide is a once-weekly peptide that activates GIP and GLP-1 receptors. It is FDA-approved as Mounjaro for type 2 diabetes and as Zepbound for weight management and obstructive sleep apnea in adults with obesity1FDAMOUNJARO, MOUNJARO KWIKPEN prescribing information: Indications and Usage. FDA-approved labeling via openFDA/DailyMed, version effective 2026-08-27.,2FDAZEPBOUND, ZEPBOUND KWIKPEN prescribing information: Indications and Usage. FDA-approved labeling via openFDA/DailyMed, version effective 2026-08-28.. In SURMOUNT-1, adults with obesity lost 15.0–20.9% of body weight at 72 weeks versus 3.1% on placebo3PubMedTirzepatide Once Weekly for the Treatment of Obesity. Jastreboff AM et al. N Engl J Med. 2022.. Its half-life is about five days4PubMedPopulation pharmacokinetics of the GIP/GLP receptor agonist tirzepatide. Schneck K & Urva S CPT Pharmacometrics Syst Pharmacol. 2024..

PubMed records
2,640962 reviews
Trial publications
147136 tagged RCT
Registered studies
300199 active · 57 phase 3
Molecular weight
4,813g/mol · PubChem
Evidence grade
AApproved / regulatory-grade

Key findings

  1. In SURMOUNT-1 (obesity, no diabetes), 72-week weight change was −15.0%, −19.5% and −20.9% at 5, 10 and 15 mg, versus −3.1% with placebo; 57% of the 15 mg group lost 20% or more3.
  2. In SURMOUNT-5, the only head-to-head obesity trial, tirzepatide produced −20.2% versus −13.7% with semaglutide at 72 weeks5PubMedTirzepatide as Compared with Semaglutide for the Treatment of Obesity. Aronne LJ et al. N Engl J Med. 2025..
  3. In SURPASS-2 (type 2 diabetes), all three doses lowered HbA1c more than semaglutide 1 mg (−2.01 to −2.30 vs −1.86 points)6PubMedTirzepatide versus Semaglutide Once Weekly in Patients with Type 2 Diabetes. Frías JP et al. N Engl J Med. 2021..
  4. In people with obesity and prediabetes treated for three years, 1.3% developed type 2 diabetes on tirzepatide versus 13.3% on placebo7PubMedTirzepatide for Obesity Treatment and Diabetes Prevention. Jastreboff AM et al. N Engl J Med. 2025..
  5. Stopping treatment led to regain: after a 36-week lead-in, participants switched to placebo regained 14.0% while those who continued lost a further 5.5%8PubMedContinued Treatment With Tirzepatide for Maintenance of Weight Reduction in Adults With Obesity: The SURMOUNT-4 Randomized Clinical Trial. Aronne LJ et al. JAMA. 2024..

Written by Residue Editorial Team

Reviewed by Residue Editorial Team · source-by-source check,

First published

Last updated

Registry data · How we grade · Markdown + sources

What is Tirzepatide, chemically?

Identifiers retrieved from PubChem.
PubChem CID166567236 “CID 166567236”
FormulaC225H348N48O68
Molecular weight4,813 g/mol
CAS (as listed)2023788-19-2
InChIKeyBTSOGEDATSQOAF-MCNPHUAVSA-N
Half-life (reported)About 5 days, supporting once-weekly dosing4
Route in trialsOnce-weekly subcutaneous injection
OriginatorEli Lilly and Company
MechanismDual agonist at GIP and GLP-1 receptors
Figure 1. Elemental composition of Tirzepatide from its PubChem molecular formula C225H348N48O68 (689 atoms; CID 166567236). PubChem does not publish a residue-level sequence for this record, so none is shown — we do not transcribe sequences from secondary sources.

How does Tirzepatide work?

Tirzepatide is a single synthetic peptide engineered to act on two incretin receptors: the glucose-dependent insulinotropic polypeptide (GIP) receptor and the glucagon-like peptide-1 (GLP-1) receptor. FDA labeling describes both Mounjaro and Zepbound as GIP receptor and GLP-1 receptor agonists1,2. GIP and GLP-1 are both incretins — gut hormones that amplify insulin secretion after a meal — which is why the program was first developed for type 2 diabetes9PubMedEfficacy and safety of a novel dual GIP and GLP-1 receptor agonist tirzepatide in patients with type 2 diabetes (SURPASS-1): a double-blind, randomised, phase 3 trial. Rosenstock J et al. Lancet. 2021..

A population pharmacokinetic model pooled from 19 studies described a two-compartment profile with a half-life of about five days, enabling once-weekly dosing; covariate analysis suggested dose adjustment by demographic subgroup was unnecessary4.

What did the SURPASS trials find in type 2 diabetes?

SURPASS-1 randomized 478 adults with type 2 diabetes managed by diet and exercise alone. At 40 weeks, HbA1c fell by 1.87, 1.89 and 2.07 percentage points with 5, 10 and 15 mg, against a rise of 0.04 with placebo; 31–52% of tirzepatide participants reached an HbA1c below 5.7%, versus 1% on placebo9.

SURPASS-2 then compared tirzepatide with the active comparator semaglutide 1 mg in an open-label 40-week trial of 1,879 patients (mean baseline HbA1c 8.28%). All tirzepatide doses were non-inferior and superior on HbA1c (−2.01, −2.24 and −2.30 points versus −1.86), and weight fell 1.9 to 5.5 kg more than with semaglutide6. Hypoglycemia below 54 mg/dL occurred in 0.2–1.7% of tirzepatide participants and 0.4% with semaglutide.

What did the SURMOUNT trials find in obesity?

SURMOUNT-1 enrolled adults with obesity, or overweight with a weight-related condition, without diabetes; mean baseline weight was 104.8 kg. Mean weight change at 72 weeks was −15.0% (5 mg), −19.5% (10 mg) and −20.9% (15 mg) against −3.1% with placebo, and half or more of the 10 and 15 mg groups lost at least 20%3. The prediabetes subgroup continued to 176 weeks, with weight change of −12.3% to −19.7% versus −1.3% and a hazard ratio of 0.07 for progression to type 2 diabetes7.

SURMOUNT-4 tested what happens after weight loss. All participants took tirzepatide for 36 weeks (mean −20.9%), then were randomized to continue or switch to placebo. From week 36 to 88, the continued group lost a further 5.5% while the placebo group regained 14.0%; 89.5% of those continuing kept at least 80% of their lead-in loss, versus 16.6% on placebo8.

SURMOUNT-OSA ran two 52-week trials in people with moderate-to-severe obstructive sleep apnea and obesity. The apnea–hypopnea index fell by 25.3 and 29.3 events per hour with tirzepatide against 5.3 and 5.5 with placebo, with improvements in hypoxic burden, hsCRP and systolic blood pressure10PubMedTirzepatide for the Treatment of Obstructive Sleep Apnea and Obesity. Malhotra A et al. N Engl J Med. 2024..

SURMOUNT-5 is the first randomized head-to-head obesity trial against semaglutide. In 751 adults without diabetes, weight change at 72 weeks was −20.2% with tirzepatide and −13.7% with semaglutide; waist circumference fell 18.4 cm versus 13.0 cm5.

What adverse events were reported in trials?

The dominant adverse events are gastrointestinal and cluster during dose escalation. Pooling SURPASS-1 to -5 (6,263 participants), nausea was reported in 12–24%, diarrhea in 12–22% and vomiting in 2–13%; the events were transient and mild to moderate. Weight loss was similar whether or not participants reported nausea, vomiting or diarrhea, and mediation analysis attributed under 6% of the weight difference versus comparators to these effects11PubMedGastrointestinal adverse events and weight reduction in people with type 2 diabetes treated with tirzepatide in the SURPASS clinical trials. Patel H et al. Diabetes Obes Metab. 2024..

In SURMOUNT-1, adverse events led to treatment discontinuation in 4.3% (5 mg), 7.1% (10 mg) and 6.2% (15 mg) of participants versus 2.6% with placebo3. The FDA label carries the full list of warnings and should be read for any clinical question2.

Is Tirzepatide FDA-approved?

Table 1. Regulatory status of Tirzepatide in the United States — from Drugs@FDA (openFDA) and FDA’s bulk-substance compounding categories, as fetched.
RecordStatusSource
ZEPBOUND, ZEPBOUND KWIKPEN, ZEPBOUND (AUTOINJECTOR)
NDA217806 · ELI LILLY AND CO		 FDA-approved original approval 2023-11-08
SOLUTION SUBCUTANEOUS		 13
MOUNJARO, MOUNJARO KWIKPEN, MOUNJARO (AUTOINJECTOR)
NDA215866 · ELI LILLY AND CO		 FDA-approved original approval 2022-05-13
SOLUTION SUBCUTANEOUS		 12
Shortage & compounding FDA declared the national shortage of tirzepatide injection products resolved; the temporary enforcement-discretion windows for compounded copies have since ended. 14

Two branded products contain tirzepatide: Mounjaro, approved in May 202212FDADrugs@FDA: MOUNJARO, MOUNJARO KWIKPEN, MOUNJARO (AUTOINJECTOR) (NDA215866). ELI LILLY AND CO; original approval 2022-05-13; Prescription., and Zepbound, approved in November 202313FDADrugs@FDA: ZEPBOUND, ZEPBOUND KWIKPEN, ZEPBOUND (AUTOINJECTOR) (NDA217806). ELI LILLY AND CO; original approval 2023-11-08; Prescription.. Zepbound's labeling advises against co-administration with other tirzepatide-containing products or any GLP-1 receptor agonist2.

During the 2022–2024 shortage, compounded tirzepatide was widely sold. FDA has since declared the shortage resolved; its April 2026 statement says tirzepatide is not on the 503B bulks list or the drug-shortage list, which limits outsourcing-facility compounding, and restates the "essentially a copy" limits for 503A pharmacies14FDAFDA clarifies policies for compounders as national GLP-1 supply begins to stabilize. U.S. FDA, content current as of 04/01/2026..

What is still unknown?

  • Cardiovascular outcomes in obesity without diabetes. The label's cardiovascular indication is for type 2 diabetes1; trial registries list further outcome studies15TrialClinicalTrials.gov registry search: tirzepatide OR LY3298176. 300 registered studies at fetch..
  • Maintenance. SURMOUNT-4 shows regain after withdrawal8; the best long-term strategy is still being studied.

What effects has Tirzepatide shown, by body system?

Each row is graded separately using the Residue evidence scale: a compound can carry an A for one use and a D for another.

Table 2. Research-observed effects of Tirzepatide by body system, with the strongest evidence available for each.
SystemWhat was observedGrade
Body weightChronic weight management in adults with obesity, or overweight with a comorbidity, is an approved indication2; −20.9% at 72 weeks with 15 mg in SURMOUNT-13. A
Glycemic controlApproved to improve glycemic control in type 2 diabetes1; HbA1c −1.87 to −2.07 points at 40 weeks as monotherapy9. A
Sleep apneaApproved for moderate-to-severe OSA in adults with obesity2; AHI fell by 25.3–29.3 events/hour versus about 5 on placebo10. A
CardiovascularMounjaro's label includes reducing major adverse cardiovascular events in adults with type 2 diabetes at high risk1. A
Diabetes preventionProgression to type 2 diabetes 1.3% versus 13.3% over 176 weeks in prediabetes (hazard ratio 0.07)7. B
Gastrointestinal (adverse)Nausea 12–24%, diarrhea 12–22% and vomiting 2–13% across SURPASS-1 to -5, mostly transient and mild to moderate11. A

How much research is there on Tirzepatide?

05951189 1994: 1 records 1994 1995: 0 records 1995 1996: 0 records 1997: 0 records 1998: 0 records 1999: 0 records 2000: 0 records 2000 2001: 0 records 2002: 0 records 2003: 0 records 2004: 0 records 2005: 0 records 2005 2006: 1 records 2007: 0 records 2008: 0 records 2009: 0 records 2010: 0 records 2010 2011: 0 records 2012: 2 records 2013: 0 records 2014: 0 records 2015: 0 records 2015 2016: 0 records 2017: 0 records 2018: 2 records 2019: 0 records 2020: 11 records 2020 2021: 37 records 2022: 113 records 2023: 221 records 2024: 394 records 2025: 902 records 2025 2026: 1189 records (year to date) 2026
Figure 2. PubMed records per publication year matching (tirzepatide[tiab] OR LY3298176[tiab]) — 2,640 in total; peak 1189 in 2026. The 2026 bar is year-to-date (hatched). Volume of literature is not evidence of efficacy. Run this query on PubMed.
Registered studies of Tirzepatide by phase and status
PhaseStudiesBreakdown
Early phase 1 6
0 completed, 6 active or recruiting, 0 stopped, 0 other
Phase 1 34
24 completed, 10 active or recruiting, 0 stopped, 0 other
Phase 2 73
16 completed, 53 active or recruiting, 2 stopped, 2 other
Phase 3 57
31 completed, 26 active or recruiting, 0 stopped, 0 other
Phase 4 48
5 completed, 41 active or recruiting, 2 stopped, 0 other
Not applicable 29
0 completed, 27 active or recruiting, 0 stopped, 2 other
Observational 53
15 completed, 36 active or recruiting, 2 stopped, 0 other
Figure 3. 300 studies on ClinicalTrials.gov match the registry search tirzepatide OR LY3298176. Multi-phase studies are counted at their highest phase. Open the full trial feed

Compare and continue

Questions readers ask

What is tirzepatide approved for?

As Mounjaro: glycemic control in type 2 diabetes (adults and children 10 and older) and reducing major cardiovascular events in adults with type 2 diabetes at high risk1. As Zepbound: chronic weight management in adults with obesity or overweight with a weight-related condition, and moderate-to-severe obstructive sleep apnea in adults with obesity2.

What are the most common side effects of tirzepatide?

Gastrointestinal events. Across the SURPASS trials, nausea occurred in 12–24%, diarrhea in 12–22% and vomiting in 2–13% of participants, mostly transient and mild to moderate11. In SURMOUNT-1, adverse events led to discontinuation in 4.3–7.1% on tirzepatide versus 2.6% on placebo3.

What is the half-life of tirzepatide?

About five days, according to a population pharmacokinetic model built from 19 pooled studies4.

Is tirzepatide better than semaglutide?

For weight in adults with obesity without diabetes, SURMOUNT-5 found greater reduction with tirzepatide (−20.2% vs −13.7% at 72 weeks)5. In type 2 diabetes, SURPASS-2 found larger HbA1c and weight reductions than semaglutide 1 mg6. Semaglutide has a dedicated cardiovascular-outcomes trial in people without diabetes16. See the full comparison.

What happens when tirzepatide is stopped?

In SURMOUNT-4, participants switched to placebo after 36 weeks regained 14.0% of body weight by week 88, while those who continued lost a further 5.5%8.

Can tirzepatide still be compounded?

FDA declared the tirzepatide shortage resolved, and its April 2026 statement notes tirzepatide is not on the 503B bulks list or the drug-shortage list, which restricts outsourcing-facility compounding14.

What is tirzepatide?

Tirzepatide is a once-weekly peptide that activates both GIP and GLP-1 receptors. It is FDA-approved as Mounjaro for type 2 diabetes and as Zepbound for weight management and obstructive sleep apnea with obesity1,2.

References

Every source below was retrieved from its official API or page and cached on the data-edition date. Numbers match the margin notes.

  1. 1 FDA MOUNJARO, MOUNJARO KWIKPEN prescribing information: Indications and Usage. FDA-approved labeling via openFDA/DailyMed, version effective 2026-08-27.
  2. 2 FDA ZEPBOUND, ZEPBOUND KWIKPEN prescribing information: Indications and Usage. FDA-approved labeling via openFDA/DailyMed, version effective 2026-08-28.
  3. 3 PubMed Jastreboff AM, Aronne LJ, Ahmad NN, et al. Tirzepatide Once Weekly for the Treatment of Obesity. N Engl J Med 2022. PMID 35658024; doi:10.1056/NEJMoa2206038.
  4. 4 PubMed Schneck K, Urva S. Population pharmacokinetics of the GIP/GLP receptor agonist tirzepatide. CPT Pharmacometrics Syst Pharmacol 2024. PMID 38356317; doi:10.1002/psp4.13099.
  5. 5 PubMed Aronne LJ, Horn DB, le Roux CW, et al. Tirzepatide as Compared with Semaglutide for the Treatment of Obesity. N Engl J Med 2025. PMID 40353578; doi:10.1056/NEJMoa2416394.
  6. 6 PubMed Frías JP, Davies MJ, Rosenstock J, et al. Tirzepatide versus Semaglutide Once Weekly in Patients with Type 2 Diabetes. N Engl J Med 2021. PMID 34170647; doi:10.1056/NEJMoa2107519.
  7. 7 PubMed Jastreboff AM, le Roux CW, Stefanski A, et al. Tirzepatide for Obesity Treatment and Diabetes Prevention. N Engl J Med 2025. PMID 39536238; doi:10.1056/NEJMoa2410819.
  8. 8 PubMed Aronne LJ, Sattar N, Horn DB, et al. Continued Treatment With Tirzepatide for Maintenance of Weight Reduction in Adults With Obesity: The SURMOUNT-4 Randomized Clinical Trial. JAMA 2024. PMID 38078870; doi:10.1001/jama.2023.24945.
  9. 9 PubMed Rosenstock J, Wysham C, Frías JP, et al. Efficacy and safety of a novel dual GIP and GLP-1 receptor agonist tirzepatide in patients with type 2 diabetes (SURPASS-1): a double-blind, randomised, phase 3 trial. Lancet 2021. PMID 34186022; doi:10.1016/S0140-6736(21)01324-6.
  10. 10 PubMed Malhotra A, Grunstein RR, Fietze I, et al. Tirzepatide for the Treatment of Obstructive Sleep Apnea and Obesity. N Engl J Med 2024. PMID 38912654; doi:10.1056/NEJMoa2404881.
  11. 11 PubMed Patel H, Khunti K, Rodbard HW, et al. Gastrointestinal adverse events and weight reduction in people with type 2 diabetes treated with tirzepatide in the SURPASS clinical trials. Diabetes Obes Metab 2024. PMID 37853960; doi:10.1111/dom.15333.
  12. 12 FDA Drugs@FDA: MOUNJARO, MOUNJARO KWIKPEN, MOUNJARO (AUTOINJECTOR) (NDA215866). ELI LILLY AND CO; original approval 2022-05-13; Prescription.
  13. 13 FDA Drugs@FDA: ZEPBOUND, ZEPBOUND KWIKPEN, ZEPBOUND (AUTOINJECTOR) (NDA217806). ELI LILLY AND CO; original approval 2023-11-08; Prescription.
  14. 14 FDA FDA clarifies policies for compounders as national GLP-1 supply begins to stabilize. U.S. FDA, content current as of 04/01/2026.
  15. 15 ClinicalTrials.gov ClinicalTrials.gov registry search: tirzepatide OR LY3298176. 300 registered studies at fetch.
  16. 16 PubMed Lincoff AM, Brown-Frandsen K, Colhoun HM, et al. Semaglutide and Cardiovascular Outcomes in Obesity without Diabetes. N Engl J Med 2023. PMID 37952131; doi:10.1056/NEJMoa2307563.