InvestigationalHuman evidence

Retatrutide

Also referred to as LY3437943, Triple-G

An investigational triple agonist with a published phase 2 trial. It is not approved, and phase 3 outcome data are not established.

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

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Human studies

Animal / in vitro

Graded claims

338

Participants

Derived from qualifying human evidence

Most commonly studied duration: 48 weeks. Most frequently reported duration among 1 qualifying human study with a stated duration.
Longest qualifying human study: 48 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

Agonises GIP, GLP-1, and glucagon receptors. The glucagon component is proposed to increase energy expenditure in addition to the appetite effects of the incretin components.

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

CPreliminaryModerate confidenceHuman evidence

In a single phase 2 trial, retatrutide was associated with dose-dependent weight reduction over 48 weeks.

What is not established

No phase 3 outcome data. Long-term and cardiovascular safety are unestablished. A dose-dependent heart-rate increase was reported and is unresolved.

Supporting sources (2)

Randomised controlled trialHuman Identifier verified

Triple–Hormone-Receptor Agonist Retatrutide for Obesity — A Phase 2 Trial

Jastreboff AM, Kaplan LM, Frías JP, et al. · New England Journal of Medicine · 2023 · n = 338

Population: Adults with BMI ≥30, or ≥27 with at least one weight-related condition
Endpoint: Percentage change in body weight at 24 and 48 weeks
Route: Subcutaneous
Quantity as reported: 1 mg, 4 mg, 8 mg, or 12 mg weekly
Frequency: Once weekly
Duration: 48 weeks

Result. Mean weight reduction at 48 weeks reached −24.2% in the highest-dose group versus −2.1% with placebo.

Adverse events. Dose-dependent gastrointestinal events; dose-dependent increases in heart rate were reported that peaked and then declined.

Limitations. Phase 2, 338 participants, 48 weeks. Not a phase 3 outcome trial; long-term safety and cardiovascular outcomes are not established.

PMID37366315 DOI10.1056/NEJMoa2301972 NCTNCT04881760

Meta-analysisHuman Identifier verified

Effects of once-weekly subcutaneous retatrutide on weight and metabolic markers: a systematic review and meta-analysis of randomized controlled trials

Multiple · Systematic review / meta-analysis · 2024

Population: Pooled participants from randomised retatrutide trials
Endpoint: Pooled weight and metabolic marker change
Route: Subcutaneous
Quantity as reported: Pooled across trial arms
Frequency: Once weekly

Result. Pooled analysis reported significant weight and metabolic marker changes versus comparator.

Adverse events. Pooled gastrointestinal event rates consistent with the individual trials.

Limitations. Small number of constituent trials; heterogeneity in dose and duration; dominated by a single phase 2 programme.

PMID39318607

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

Triple–Hormone-Receptor Agonist Retatrutide for Obesity — A Phase 2 Trial

Jastreboff AM, Kaplan LM, Frías JP, et al. · New England Journal of Medicine · 2023 · n = 338

Population: Adults with BMI ≥30, or ≥27 with at least one weight-related condition
Endpoint: Percentage change in body weight at 24 and 48 weeks
Route: Subcutaneous
Quantity as reported: 1 mg, 4 mg, 8 mg, or 12 mg weekly
Frequency: Once weekly
Duration: 48 weeks

Result. Mean weight reduction at 48 weeks reached −24.2% in the highest-dose group versus −2.1% with placebo.

Adverse events. Dose-dependent gastrointestinal events; dose-dependent increases in heart rate were reported that peaked and then declined.

Limitations. Phase 2, 338 participants, 48 weeks. Not a phase 3 outcome trial; long-term safety and cardiovascular outcomes are not established.

PMID37366315 DOI10.1056/NEJMoa2301972 NCTNCT04881760

Meta-analysisHuman Identifier verified

Effects of once-weekly subcutaneous retatrutide on weight and metabolic markers: a systematic review and meta-analysis of randomized controlled trials

Multiple · Systematic review / meta-analysis · 2024

Population: Pooled participants from randomised retatrutide trials
Endpoint: Pooled weight and metabolic marker change
Route: Subcutaneous
Quantity as reported: Pooled across trial arms
Frequency: Once weekly

Result. Pooled analysis reported significant weight and metabolic marker changes versus comparator.

Adverse events. Pooled gastrointestinal event rates consistent with the individual trials.

Limitations. Small number of constituent trials; heterogeneity in dose and duration; dominated by a single phase 2 programme.

PMID39318607

Pharmacology

Reported parameters

Half-life

6.0 days

Approximately 6 days as reported in early-phase work.

Visualise this half-life →

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

Investigational. Not approved for any indication. Material sold outside a clinical trial is not the trial product.

Storage as documented

No approved storage labelling exists for this investigational compound.

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.

Dose-dependent gastrointestinal events in the phase 2 trial
Dose-dependent heart-rate increase reported, which peaked and then declined
Long-term and cardiovascular safety are not established

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.

A single published phase 2 trial of 338 participants over 48 weeks
No phase 3 outcome data; no regulatory approval
Enthusiasm in non-scientific sources substantially exceeds the strength of the published evidence

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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