Retatrutide
Also referenced as: LY3437943, GIP/GLP-1/glucagon triple agonist
An investigational triple incretin agonist that produced very large weight reductions in phase 2 research.
Quick answers
- What is retatrutide?
- Retatrutide is an investigational triple agonist that acts on GLP-1, GIP and glucagon receptors. It is being developed by Eli Lilly for obesity and related conditions.
- What are the side effects of retatrutide?
- In phase 2 trials the most common were nausea, diarrhoea, vomiting and constipation, plus a dose-related rise in heart rate. Long-term safety is still being studied.
- Is retatrutide legal or FDA approved?
- No. Retatrutide is not approved anywhere and is available only within clinical trials. Products sold online are unregulated.
- Does retatrutide work?
- Early results are strong: a phase 2 trial reported average weight loss of about 24% at 48 weeks on the highest dose. Phase 3 trials are ongoing.
Educational summary, not medical advice. Sources are listed below.
- Evidence grade
- BModerate Human Evidence
Moderate Human Evidence
- Regulatory status
- Clinical Trials
An investigational compound in active clinical development. It is not approved for any indication anywhere, and material sold as research-use-only retatrutide is not a medicine.
- Human data
- Yes
Registered clinical trials exist
- Last reviewed
- September 1, 2026
Overview
Retatrutide adds glucagon receptor agonism to the GIP and GLP-1 activity seen with tirzepatide. Glucagon signalling is of interest because it may increase energy expenditure and reduce liver fat, at the cost of a more complex safety profile.
Public discussion has run far ahead of the evidence base. At last review the compound had published phase 2 results and ongoing phase 3 trials — impressive early data, not an established therapy.
Why It's Being Studied
- Whether adding glucagon agonism increases weight loss beyond dual agonists.
- Hepatic fat reduction in metabolic dysfunction-associated steatotic liver disease.
- Glycaemic control in type 2 diabetes and knee osteoarthritis pain associated with obesity.
Mechanism of Action
It acts on three metabolic hormone receptors at once — two that influence insulin and appetite, and one that influences how much energy the body burns and how the liver handles fat.
Retatrutide is a single peptide agonist at GIP, GLP-1 and glucagon receptors with fatty-acid modification supporting weekly dosing. Glucagon receptor agonism is proposed to raise resting energy expenditure and promote hepatic lipid oxidation, while incretin agonism offsets glucagon's hyperglycaemic tendency.
The incretin signalling pathway
Tap each stage to see what happens.
Background: Metabolic Health & Weight Management
Metabolic peptide research centres on the gut–brain–pancreas axis: hormones released after meals (incretins such as GLP-1 and GIP) that shape insulin release, stomach emptying and appetite.
This is the most clinically mature corner of peptide science. Several incretin-based medicines have large randomised trials behind them, which makes the gap between approved drugs and unapproved research compounds especially important to understand.
Research Areas & Routes Studied
- Body weight
- Hepatic fat
- Glycaemic control
- Subcutaneous injection (in clinical trials)
Evidence Summary
Published phase 2 randomised data in humans with large effect sizes, but phase 3 programmes were still in progress at last review and no regulatory approval exists.
Higher tiers carry more weight. Filled tiers have evidence for Retatrutide; tap to read it.
- A phase 2 randomised trial reported mean weight reduction around 24% at 48 weeks at the highest dose, with dose-dependent results.
- Phase 3 TRIUMPH programme trials were recruiting or ongoing at last review; outcomes were not yet published.
2 cited sources spanning 2023–2023.
- Phase 2 trial1
- Regulatory document1
Human clinical evidence
- A phase 2 randomised trial reported mean weight reduction around 24% at 48 weeks at the highest dose, with dose-dependent results.
Clinical trials
- Phase 3 TRIUMPH programme trials were recruiting or ongoing at last review; outcomes were not yet published.
Anecdotal / community information
- Large volumes of unverified community protocols circulate. No established human dosing protocol outside clinical trials exists.
Reported Adverse Events in Research
- Predominantly gastrointestinal in phase 2: nausea, vomiting, diarrhoea, constipation.
- Dose-dependent heart rate increases were reported.
- Long-term safety is unknown; no post-marketing surveillance exists.
Limitations of Current Evidence
- Phase 2 evidence only at last review, in relatively small populations over under a year.
- No approved label, so any dosing information comes from trial protocols rather than clinical practice.
How to Read This Research
- Was weight loss measured against placebo, and over how many weeks?
- How much of the lost weight was lean mass rather than fat?
- What happened after the compound was stopped?
- Were cardiovascular, kidney or liver outcomes measured — or only weight?
- Percentage body-weight change versus placebo is the headline trial metric; absolute kilograms depend on starting weight.
- Gastrointestinal side effects are dose-related and usually reported by escalation phase.
- Compare approved-drug trial data with unapproved compounds carefully — a shared receptor is not shared evidence.
- Incretin
- A gut hormone that increases insulin release after eating.
- HbA1c
- A blood marker of average glucose over roughly three months.
- Agonist
- A molecule that activates a receptor.
Compare With Other Compounds
| Retatrutide | Semaglutide | |
|---|---|---|
| Evidence grade | B — Moderate Human Evidence | A — Strong Clinical Evidence |
| Regulatory status | Clinical Trials | FDA Approved for Specific Indication |
| Human data | Yes | Yes |
| Clinical trials | Registered trials exist | Registered trials exist |
| Research routes | Subcutaneous injection (in clinical trials) | Subcutaneous injection, Oral tablet (approved form) |
| Cited sources | 2 | 4 |
Frequently Asked Questions
Documented Research Protocols
Retatrutide — phase 2 trial protocol as published
Summarise the escalation and maintenance structure reported in the published phase 2 obesity trial.
View documented protocol
Why It Is Used
- Metabolic Health
Weight Loss and Liver Fat
The most common reason people look at peptides at all: sustained appetite reduction, and what trials report about liver fat alongside it.
Read the case study
Research References
- Phase 2 trial2023
Triple-Hormone-Receptor Agonist Retatrutide for Obesity — A Phase 2 Trial
Jastreboff AM, et al. · New England Journal of Medicine- Population
- 338 adults with obesity or overweight with comorbidity
- Main finding
- Mean weight reduction of approximately 24% at 48 weeks with the highest dose.
- Limitations
- Phase 2 size and duration; not an outcome trial.
- Regulatory document
Registered retatrutide trials