FDA-approvedHuman evidence

Tirzepatide

Also referred to as Mounjaro, Zepbound, LY3298176

A dual incretin receptor agonist with large randomised evidence including a 176-week readout that also reported post-withdrawal weight regain.

Molecule class: Dual GIP/GLP-1 receptor agonist
Category: Incretin
Last evidence review: 2026-08-23

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Human studies

Animal / in vitro

Graded claims

5,078

Participants

Derived from qualifying human evidence

Most commonly studied duration: 72 weeks. Most frequently reported duration among 2 qualifying human studies with a stated duration.
Longest qualifying human study: 176 weeks. Longest duration among qualifying human studies with a stated duration.

These figures are computed from the study records shown below. Records without a verified source identifier are excluded from the calculation.

Mechanism

What is being studied

Simultaneously agonises GIP and GLP-1 receptors. The contribution of the GIP component to the observed effect is an area of continuing scientific debate.

Evidence

Claims, graded individually

Each statement below carries its own evidence level, its own confidence rating, and its own account of what remains unestablished. A compound does not have a single grade.

Metabolic & Body-Composition Research

AStrongHigh confidenceHuman evidence

Once-weekly tirzepatide was associated with dose-dependent body-weight reduction over 72 weeks versus placebo in adults with obesity or overweight without diabetes.

What is not established

Comparative effectiveness against every alternative, and effects in populations excluded from the trials, are not fully established.

Supporting sources (2)

Randomised controlled trialHuman Identifier verified

Tirzepatide Once Weekly for the Treatment of Obesity

Jastreboff AM, Aronne LJ, Ahmad NN, et al. · New England Journal of Medicine · 2022 · n = 2,539

Population: Adults with BMI ≥30, or ≥27 with a weight-related complication; without diabetes
Endpoint: Percentage change in body weight at week 72
Route: Subcutaneous
Quantity as reported: 5 mg, 10 mg, or 15 mg weekly
Frequency: Once weekly
Duration: 72 weeks

Result. Mean percentage weight change was −15.0%, −19.5%, and −20.9% at 5 mg, 10 mg, and 15 mg respectively, versus −3.1% with placebo.

Adverse events. Predominantly gastrointestinal (nausea, diarrhoea, constipation, vomiting), mostly mild to moderate and occurring during escalation.

Limitations. Excluded participants with diabetes; lifestyle intervention in all arms; does not establish durability after discontinuation.

PMID35658024 DOI10.1056/NEJMoa2206038 NCTNCT04184622

Randomised controlled trialHuman Identifier verified

Tirzepatide for Obesity Treatment and Diabetes Prevention

Jastreboff AM, le Roux CW, Stefanski A, et al. · New England Journal of Medicine · 2024 · n = 2,539

Population: Adults with obesity or overweight and prediabetes
Endpoint: Progression to type 2 diabetes and sustained weight change over 176 weeks
Route: Subcutaneous
Quantity as reported: Maximum tolerated dose 10 mg or 15 mg weekly
Frequency: Once weekly
Duration: 176 weeks

Result. Reported substantially lower progression to type 2 diabetes versus placebo with sustained weight reduction over the treatment period; weight regain was observed after treatment withdrawal.

Adverse events. Consistent with the established gastrointestinal profile of the class.

Limitations. Prediabetes population only; the post-withdrawal regain finding is directly relevant to any assumption that effects persist after stopping.

PMID39536238 DOI10.1056/NEJMoa2410819 NCTNCT04184622

Last evidence review: 2026-08-23

Metabolic & Body-Composition Research

AStrongHigh confidenceHuman evidence

In adults with obesity and prediabetes, tirzepatide was associated with reduced progression to type 2 diabetes over 176 weeks, with weight regain reported after withdrawal.

What is not established

The finding is specific to a prediabetes population.

Supporting sources (1)

Randomised controlled trialHuman Identifier verified

Tirzepatide for Obesity Treatment and Diabetes Prevention

Jastreboff AM, le Roux CW, Stefanski A, et al. · New England Journal of Medicine · 2024 · n = 2,539

Population: Adults with obesity or overweight and prediabetes
Endpoint: Progression to type 2 diabetes and sustained weight change over 176 weeks
Route: Subcutaneous
Quantity as reported: Maximum tolerated dose 10 mg or 15 mg weekly
Frequency: Once weekly
Duration: 176 weeks

Result. Reported substantially lower progression to type 2 diabetes versus placebo with sustained weight reduction over the treatment period; weight regain was observed after treatment withdrawal.

Adverse events. Consistent with the established gastrointestinal profile of the class.

Limitations. Prediabetes population only; the post-withdrawal regain finding is directly relevant to any assumption that effects persist after stopping.

PMID39536238 DOI10.1056/NEJMoa2410819 NCTNCT04184622

Last evidence review: 2026-08-23

Human evidence

2 human studies catalogued

Human and non-human evidence are kept strictly separate. They are never pooled, averaged, or presented as a single body of support.

Randomised controlled trialHuman Identifier verified

Tirzepatide Once Weekly for the Treatment of Obesity

Jastreboff AM, Aronne LJ, Ahmad NN, et al. · New England Journal of Medicine · 2022 · n = 2,539

Population: Adults with BMI ≥30, or ≥27 with a weight-related complication; without diabetes
Endpoint: Percentage change in body weight at week 72
Route: Subcutaneous
Quantity as reported: 5 mg, 10 mg, or 15 mg weekly
Frequency: Once weekly
Duration: 72 weeks

Result. Mean percentage weight change was −15.0%, −19.5%, and −20.9% at 5 mg, 10 mg, and 15 mg respectively, versus −3.1% with placebo.

Adverse events. Predominantly gastrointestinal (nausea, diarrhoea, constipation, vomiting), mostly mild to moderate and occurring during escalation.

Limitations. Excluded participants with diabetes; lifestyle intervention in all arms; does not establish durability after discontinuation.

PMID35658024 DOI10.1056/NEJMoa2206038 NCTNCT04184622

Randomised controlled trialHuman Identifier verified

Tirzepatide for Obesity Treatment and Diabetes Prevention

Jastreboff AM, le Roux CW, Stefanski A, et al. · New England Journal of Medicine · 2024 · n = 2,539

Population: Adults with obesity or overweight and prediabetes
Endpoint: Progression to type 2 diabetes and sustained weight change over 176 weeks
Route: Subcutaneous
Quantity as reported: Maximum tolerated dose 10 mg or 15 mg weekly
Frequency: Once weekly
Duration: 176 weeks

Result. Reported substantially lower progression to type 2 diabetes versus placebo with sustained weight reduction over the treatment period; weight regain was observed after treatment withdrawal.

Adverse events. Consistent with the established gastrointestinal profile of the class.

Limitations. Prediabetes population only; the post-withdrawal regain finding is directly relevant to any assumption that effects persist after stopping.

PMID39536238 DOI10.1056/NEJMoa2410819 NCTNCT04184622

Pharmacology

Reported parameters

Half-life

5.0 days

Approximately 5 days, supporting once-weekly administration in the trials.

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Routes studied

Subcutaneous

Evidence from one route does not transfer to another. Topical, oral, and injected administration can produce entirely different exposure from the same quantity.

Regulatory status

FDA-approved products exist for type 2 diabetes and chronic weight management, with defined labelled populations.

Storage as documented

Refrigerated per approved product labelling.

Safety

Signals reported in the literature

This lists what has been reported. It is not a complete safety profile, and for several compounds in this catalogue no systematic safety surveillance exists at all.

Gastrointestinal events predominate, concentrated during dose escalation
Boxed warning regarding thyroid C-cell tumours in rodents per labelling
Pancreatitis and gallbladder events reported
Weight regain reported after treatment withdrawal in the long-term trial

Interactions

Register entries involving this compound

semaglutide ↔ tirzepatide

Redundant receptor agonism with additive gastrointestinal and gastric-emptying effects. No trial has studied these two agents together, and neither product's labelling contemplates concurrent use.

Limitations. No study has evaluated the combination. The concern is mechanistic redundancy, which is a reasoning-based conclusion rather than an observed interaction.

tirzepatide ↔ insulin

Addressed in approved labelling with the same hypoglycaemia considerations as the GLP-1 class.

Limitations. Regimen-dependent.

tirzepatide ↔ oral contraceptives

The approved labelling contains a specific advisory regarding oral contraceptives and recommends a non-oral method or an added barrier method for a defined period after initiation and each escalation.

Limitations. Consult the current labelling for the specific advisory period, which is the authoritative source.

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Limitations

What the evidence cannot tell you

Given as much prominence as the findings, because for most compounds in this category it is the more important half.

Obesity trials excluded participants with diabetes
Head-to-head evidence against every alternative is not complete
Grey-market material is not the studied product

Reference

Evidence grading key

AStrong

Multiple high-quality human trials, or strong systematic-review or meta-analytic evidence.

BModerate

Human controlled evidence exists, but replication or sample size is limited.

CPreliminary

Small human studies, observational evidence, or early-phase clinical work.

DPreclinical

Predominantly animal or in-vitro evidence. No adequate human outcome data.

EMechanistic

Biological plausibility or mechanistic reasoning without adequate outcome evidence.

XInsufficient / conflicting

Evidence is absent, irreconcilable, or too weak to support any directional statement.

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