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.
- 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.
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.
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.
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