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Retatrutide (LY3437943) is an investigational synthetic peptide reported as an agonist at three receptors: GCGR, GIPR and GLP-1R. Four publications are reviewed: a discovery report spanning cell assays, mouse work and a phase 1 study, cryo-electron microscopy structures at each receptor, and two phase 2 publications drawn from the same registered trial. No phase 3 publication is included, and the U.S. FDA states that no FDA-approved drug contains retatrutide.
Retatrutide, also identified in the literature as LY3437943, is a synthetic peptide reported to act as an agonist at three receptors at once: the glucagon receptor (GCGR), the glucose-dependent insulinotropic polypeptide receptor (GIPR), and the glucagon-like peptide-1 receptor (GLP-1R).
Most single-receptor incretin compounds engage one of these. Engaging all three is what the published work on this compound is about, and it is why the literature spans three quite different kinds of study: cell-based assays that measure receptor activity directly, structural work that images the compound bound to each receptor, and randomised human studies that record endpoints under supervision.
This page collects what those publications report, arm by arm and measurement point by measurement point, with each figure printed as its publication printed it. It does not summarise them into a single number, and it makes no statement about what any of it means for a person.
In the published literature, retatrutide is also abbreviated "RETA" (Marathe et al., 2025, PMID 40094000).
Regulatory status
The U.S. FDA states that no FDA-approved drug contains retatrutide.
Source: U.S. FDA, Drug Alerts and Statements, https://www.fda.gov/drugs/drug-alerts-and-statements/fdas-concerns-unapproved-glp-1-drugs-used-weight-loss, content current as of 2026-09-01. Verified 2026-09-24.
Mechanism under investigation
Retatrutide
Agonist
→
GLP-1 receptor
GIP receptor
Glucagon receptor
Reported as an agonist at all three receptors. In animal work, glucagon-receptor activity has been associated with increased energy expenditure, and GIP- and GLP-1-receptor activity with reduced food intake. The relative contribution of each receptor in humans is not settled by the publications listed here.
Scope of the published work
Areas investigated
Energy balance
Glycaemic regulation
Hepatic steatosis
Receptor structural biology
Models used
Cell-based receptor assays
Rodent models
Cryo-electron microscopy
Randomised human studies
Every human figure on this page was recorded in a controlled study, under supervision, using material prepared for that study. It is not the research material supplied by PepGenex, and no result here transfers to it.
Limitations
Evidence represented on this page: in vitro, animal and human. The page reviews 4 published studies, and each figure is reported for the study that published it; results are not pooled across studies.
Common questions
What is retatrutide?
Retatrutide, also identified in the literature as LY3437943, is a synthetic peptide reported to act as an agonist at three receptors at once: the glucagon receptor (GCGR), the glucose-dependent insulinotropic polypeptide receptor (GIPR), and the glucagon-like peptide-1 receptor (GLP-1R).
How does retatrutide work?
The mechanism recorded on this page is receptor agonist activity at the glucagon, GIP and GLP-1 receptors. Reported as an agonist at all three receptors.
In cell-based assays, LY3437943 showed agonist activity at the glucagon receptor (GCGR), the glucose-dependent insulinotropic polypeptide receptor (GIPR) and the glucagon-like peptide-1 receptor (GLP-1R). (Coskun et al., 2022, PMID 35985340)
Which receptors does retatrutide interact with?
The publications on this page record retatrutide as an agonist at 3 receptors: GLP-1 receptor, GIP receptor, Glucagon receptor.
In cell-based assays, LY3437943 showed agonist activity at the glucagon receptor (GCGR), the glucose-dependent insulinotropic polypeptide receptor (GIPR) and the glucagon-like peptide-1 receptor (GLP-1R). (Coskun et al., 2022, PMID 35985340)
A cryo-electron microscopy structure of retatrutide bound to GLP-1R in complex with Gs was resolved at 2.68 Å. (Li et al., 2024, PMID 39019866)
A cryo-electron microscopy structure of retatrutide bound to GIPR in complex with Gs was resolved at 3.26 Å. (Li et al., 2024, PMID 39019866)
A cryo-electron microscopy structure of retatrutide bound to GCGR in complex with Gs was resolved at 2.84 Å. (Li et al., 2024, PMID 39019866)
How is retatrutide characterized structurally?
This page records its molecular formula C221H342N46O68, molecular weight 4731.33, CAS 2381089-83-2. Its amino-acid sequence is not recorded on this page.
Its binding to each receptor has been characterized by cryo-electron microscopy:
A cryo-electron microscopy structure of retatrutide bound to GLP-1R in complex with Gs was resolved at 2.68 Å. (Li et al., 2024, PMID 39019866)
A cryo-electron microscopy structure of retatrutide bound to GIPR in complex with Gs was resolved at 3.26 Å. (Li et al., 2024, PMID 39019866)
A cryo-electron microscopy structure of retatrutide bound to GCGR in complex with Gs was resolved at 2.84 Å. (Li et al., 2024, PMID 39019866)
What clinical trials of retatrutide are registered?
A ClinicalTrials.gov search for retatrutide as an intervention returned 33 records on 2026-09-24. Selected records, by registry fields only (full entries under Registered clinical trials):
NCT03841630: phase 1, sponsor Eli Lilly and Company, 45 participants (actual), status completed.
NCT04881760: phase 2, sponsor Eli Lilly and Company, 338 participants (actual), status completed.
NCT04867785: phase 2, sponsor Eli Lilly and Company, 281 participants (actual), status completed.
NCT05929066 (TRIUMPH-1): phase 3, sponsor Eli Lilly and Company, 2,335 participants (actual), status completed.
NCT05929079 (TRIUMPH-2): phase 3, sponsor Eli Lilly and Company, 1,152 participants (actual), status completed.
NCT05882045 (TRIUMPH-3): phase 3, sponsor Eli Lilly and Company, 1,946 participants (actual), status completed.
NCT06383390: phase 3, sponsor Eli Lilly and Company, 10,000 participants (estimated), status active, not recruiting.
What has been published about retatrutide in peer-reviewed research?
This page reviews 4 published studies. Their findings are listed under Published research, each attributed to its publication:
Li et al., 2024, PMID 39019866: cryo-electron microscopy structures of retatrutide bound to the GLP-1, GIP and glucagon receptors.
Coskun et al., 2022, PMID 35985340: a discovery report covering cell-based receptor assays, studies in obese mice and a phase 1 single ascending-amount study.
Sanyal et al., 2024, PMID 38858523: a phase 2a substudy of 98 participants from the same trial (NCT04881760).
Jastreboff et al., 2023, PMID 37366315: a phase 2, randomised, double-blind, placebo-controlled trial in 338 adults, 48 weeks (NCT04881760).
What is the status of retatrutide with the U.S. FDA?
The U.S. FDA states that no FDA-approved drug contains retatrutide.
Source: U.S. FDA, Drug Alerts and Statements, https://www.fda.gov/drugs/drug-alerts-and-statements/fdas-concerns-unapproved-glp-1-drugs-used-weight-loss, content current as of 2026-09-01. Verified 2026-09-24.
What are the limitations of the evidence on retatrutide?
Evidence represented on this page: in vitro, animal and human.
The page reviews 4 published studies, and each figure is reported for the study that published it; results are not pooled across studies.
Every human figure on this page was recorded in a controlled study, under supervision, using material prepared for that study. It is not the research material supplied by PepGenex, and no result here transfers to it.
No phase 3 publication is recorded on this page. The phase 3 trials under Registered clinical trials are listed by registry fields only, with no results.
Both phase 2 publications on this page report the same registered trial, NCT04881760, and the abstract of Jastreboff et al., 2023 states that it was funded by Eli Lilly.
Findings in cells and in mice do not establish what happens in a person, and trial observations do not establish a complete safety profile.
What risks have published studies of Retatrutide reported?
3 published human studies on this page report adverse events or safety measurements. Each is listed with its publication in the adverse-events section of this page.
Trial events do not establish a complete safety profile.
What adverse events have been reported in published retatrutide studies?
Adverse events as reported in the abstracts of the published human studies on this page. Each entry is attributed to its publication.
Coskun et al., 2022, Cell Metabolism: the phase 1 single ascending-amount portion of a discovery report
Population
Not described in the abstract
Duration
Observations reported up to day 43 after a single amount given
Events reported
The abstract describes the safety and tolerability profile as similar to other incretins. It names no specific adverse event.
Citation
PMID 35985340
Jastreboff et al., 2023, New England Journal of Medicine: phase 2, randomised, double-blind, placebo-controlled trial (NCT04881760)
Population
338 adults with a body-mass index of 30 or higher, or of 27 to less than 30 with at least one weight-related condition
Duration
48 weeks
Events reported
The most common adverse events in the retatrutide groups were gastrointestinal. They were related to the amount given and were mostly mild to moderate in severity. Increases in heart rate, related to the amount given, peaked at 24 weeks and declined thereafter.
Citation
PMID 37366315
Sanyal et al., 2024, Nature Medicine: phase 2a substudy of the same trial (NCT04881760)
Population
98 participants from that trial with metabolic dysfunction-associated steatotic liver disease
Duration
48 weeks of assignment; its primary measurement was at 24 weeks
Events reported
The abstract reports no adverse-event findings, so none is recorded here.
Citation
PMID 38858523
Trial events do not establish a complete safety profile.
Published research
Grouped by the kind of study. Select one to narrow what is shown below.
Laboratory (in vitro)(1)
Laboratory (in vitro)
Structural insights into the triple agonist retatrutide bound to its three receptors
Li et al., Cell Discovery, 2024;10:77
published
A cryo-electron microscopy structure of retatrutide bound to GLP-1R in complex with Gs was resolved at 2.68 Å.
A cryo-electron microscopy structure of retatrutide bound to GIPR in complex with Gs was resolved at 3.26 Å.
A cryo-electron microscopy structure of retatrutide bound to GCGR in complex with Gs was resolved at 2.84 Å.
What this study establishes
These structures show how the compound sits in each of the three receptors, at the resolutions stated. They characterise binding at the molecular level. They report nothing about what follows in an animal or in a person, and nothing here should be read as if they did.
Laboratory (in vitro)Preclinical (animal)Human phase 1
LY3437943, a novel triple glucagon, GIP, and GLP-1 receptor agonist for glycemic control and weight reduction: From discovery to clinical proof of concept
Coskun et al., Cell Metabolism, 2022;34(9):1234-1247
published
In cell-based assays, LY3437943 showed agonist activity at the glucagon receptor (GCGR), the glucose-dependent insulinotropic polypeptide receptor (GIPR) and the glucagon-like peptide-1 receptor (GLP-1R).
In an obese mouse model, the compound was reported to reduce body weight and to improve glycaemic measures relative to control. No magnitude is stated in the abstract, and none is reproduced here.
In mice, glucagon-receptor activity was associated with increased energy expenditure, while GIPR and GLP-1R activity were associated with reduced food intake.
In the phase 1 portion, the reported safety and tolerability profile was described as comparable to that reported for other incretin receptor agonists.
In the phase 1 portion, a reduction in body weight was reported to persist to day 43 after a single amount given.
Triple hormone receptor agonist retatrutide for metabolic dysfunction-associated steatotic liver disease: a randomized phase 2a trial
Sanyal et al., Nature Medicine, 2024;30:2037-2048
published
Phase 2a substudy: randomised, double-blind and placebo-controlled, with 98 participants.
Liver fat content, relative change from baseline
Week 24 · Phase 2a substudy participants (n=98)
Arm
Reported
Lowest dose
-42.9%
Second-lowest dose
-57.0%
Second-highest dose
-81.4%
Highest dose
-82.4%
Placebo
+0.3%
Proportion reaching liver fat content below 5%
Week 24 · Phase 2a substudy participants (n=98)
Arm
Reported
Second-highest dose
79%
Highest dose
86%
What this study establishes
A reduction in liver fat content was recorded at week 24 in the arms shown above, in a substudy population enrolled and monitored under a controlled protocol. The figures describe what was measured in those arms, at that measurement point, in that population.
Limitations
These findings come from a substudy of 98 participants inside a controlled trial. They do not generalise outside that setting, and durability beyond the reported measurement point is not established by this publication.
Triple-Hormone-Receptor Agonist Retatrutide for Obesity - A Phase 2 Trial
Jastreboff et al., New England Journal of Medicine, 2023
published
Phase 2, randomised, double-blind, placebo-controlled study in adults with obesity, with four active arms and a placebo arm.
Body weight, percent change from baseline
Week 24 · Adults with obesity
Arm
Reported
Lowest dose
-7.2%
Second-lowest dose
-12.9%
Second-highest dose
-17.3%
Highest dose
-17.5%
Placebo
-1.6%
Body weight, percent change from baseline
Week 48 · Adults with obesity
Arm
Reported
Lowest dose
-8.7%
Second-lowest dose
-17.1%
Second-highest dose
-22.8%
Highest dose
-24.2%
Placebo
-2.1%
Gastrointestinal adverse events were the most frequently reported adverse events. They were related to the amount given and were most often mild to moderate in severity.
An increase in heart rate related to the amount given was reported, peaking at week 24 and declining thereafter.
Context
The week 24 and week 48 figures come from the same study and are shown as two separate tables because they are two different measurement points, not two readings of one result. Reading across them as a trend is an inference this publication does not make.
A ClinicalTrials.gov search for retatrutide as an intervention returned 33 records on 2026-09-24. The 7 listed here were selected to show how the clinical development program is organised, by phase.
Each entry shows registry fields only, as ClinicalTrials.gov listed them when fetched. None of them reports a result here. Published findings are under Published research, each with its publication.
A Phase 3, Randomized, Double-Blind, Placebo-Controlled, Event-Driven Study to Investigate the Effect of Retatrutide on the Incidence of Major Adverse Cardiovascular Events and Major Adverse Kidney Events in Participants With Body Mass Index ≥27 kg/m2 and Atherosclerotic Cardiovascular Disease and/or Chronic Kidney Disease
Sponsor
Eli Lilly and Company
Phase
Phase 3
Design
Randomized, parallel assignment, double-blind
Enrollment
10,000 (estimated)
Status
Active, not recruiting
Start
2024-04-30
Primary completion
2029-02 (estimated)
Study completion
2029-02 (estimated)
Last update posted
2026-09-24
Last verified
2026-09-24
Registrations named in the PubMed records of publications on this page: Jastreboff et al., 2023, PMID 37366315 reports registration NCT04881760. Sanyal et al., 2024, PMID 38858523 reports registration NCT04881760.
Compared with related compounds
Classification, structure, recorded targets, evidence types and FDA status only, each read from the two compounds' own pages. These comparisons do not compare study results.
The U.S. FDA states that no FDA-approved drug contains retatrutide. Source: U.S. FDA, Drug Alerts and Statements, https://www.fda.gov/drugs/drug-alerts-and-statements/fdas-concerns-unapproved-glp-1-drugs-used-weight-loss, content current as of 2026-09-01.
An FDA approved drug product containing tirzepatide exists. Source: Drugs@FDA, Applications NDA 215866 and NDA 217806.
The U.S. FDA states that no FDA-approved drug contains retatrutide. Source: U.S. FDA, Drug Alerts and Statements, https://www.fda.gov/drugs/drug-alerts-and-statements/fdas-concerns-unapproved-glp-1-drugs-used-weight-loss, content current as of 2026-09-01.
An FDA approved drug product containing semaglutide exists. Source: Drugs@FDA, Applications NDA 209637, NDA 213051, NDA 215256 and NDA 218316.
References
Published studies reviewed (4)
LY3437943, a novel triple glucagon, GIP, and GLP-1 receptor agonist for glycemic control and weight reduction: From discovery to clinical proof of concept — Coskun et al., Cell Metabolism, 2022;34(9):1234-1247
