Retatrutide
Retatrutide (LY3437943)
Research Parameters
- Typical Dose Range
- Clinical trials: 1 to 12 mg weekly (Phase II dose range). Titration schedule still being defined in Phase III.
- Half-Life
- ~6 days
- Administration Route
- Subcutaneous
Dosing information is for research purposes only and has not been evaluated by the FDA.
Retatrutide is the one the metabolic research community is watching closely right now, because the Phase II data on body weight reduction is the largest yet recorded from any GLP-class compound. 24% average weight reduction at 48 weeks at the highest dose in the Phase II trial, with the trajectory suggesting the effect hadn't yet plateaued. Phase III trials are in progress; FDA approval is the open question.
If semaglutide is dual-incretin and tirzepatide is dual-incretin, retatrutide goes one further. It's a triple agonist at GLP-1, GIP, and glucagon receptors. That third receptor (glucagon) is the key distinction in the research. Glucagon receptor agonism drives energy expenditure up, not just appetite down, potentially addressing the metabolic-adaptation problem that limits weight maintenance in other approaches. Research is also examining it in metabolic liver disease with striking early results.
For research purposes only.
Mechanism of Action
Retatrutide is a triple incretin receptor agonist: GLP-1, GIP, and glucagon. The glucagon component is what separates it from tirzepatide and semaglutide mechanistically, and it's the component the research literature attributes most of the additional effect size to. Unlike GLP-1 and GIP (which primarily reduce caloric intake), glucagon agonism increases basal energy expenditure.
Citations
Frequently Asked Questions
- What is retatrutide used for in research?
Research focuses on obesity, type 2 diabetes, and metabolic liver disease (MASH). Phase III trials are in progress. Weight loss effect sizes in the Phase II data are the largest recorded from any compound in this class. For research purposes only.
- How does retatrutide compare to tirzepatide and semaglutide?
Semaglutide is a GLP-1 agonist; tirzepatide is a GLP-1/GIP dual agonist; retatrutide is a GLP-1/GIP/glucagon triple agonist. Each added receptor expands the mechanism. Phase II weight loss numbers scale accordingly, though retatrutide has not yet completed Phase III. For research purposes only.
- Why does the glucagon receptor component matter in retatrutide research?
GLP-1 and GIP primarily reduce caloric intake. Glucagon receptor agonism increases energy expenditure. Research suggests the combination addresses both sides of the energy balance equation, which could reduce the metabolic adaptation that limits long-term weight maintenance in mono- and dual-agonist approaches. For research purposes only.