Compound Guide• 8 min read
GLP-3 / Retatrutide: Triple GIP/GLP-1/Glucagon Agonist Research Brief
Retatrutide (LY3437943) is a once-weekly triple hormone receptor agonist that activates GIP, GLP-1, and glucagon receptors from a single molecule. It is sometimes informally referred to as 'GLP-3' because it represents the third major generation in the GLP-class metabolic peptide lineage after semaglutide (GLP-1) and tirzepatide (GIP/GLP-1).
Why retatrutide is called 'GLP-3'
The 'GLP-3' label is informal industry shorthand, not an official receptor designation. It captures the progression of the class:
- Semaglutide — single GLP-1 receptor agonist
- Tirzepatide — dual GIP + GLP-1 receptor agonist
- Retatrutide — triple GIP + GLP-1 + glucagon receptor agonist
Mechanism of action
Retatrutide is a single 39-amino-acid molecule engineered to activate three distinct class B G-protein-coupled receptors. GLP-1 agonism slows gastric emptying and enhances glucose-dependent insulin release; GIP agonism contributes to insulin sensitization and adipose modulation; glucagon agonism increases resting energy expenditure and hepatic lipid mobilization.
Structural work (Nature, 2024) has resolved how a single peptide can manifest balanced triple agonism across the three receptors.
Clinical-trial data
- Phase 2 (TRIUMPH-1): 24.2 % mean body-weight reduction at 48 weeks with the 12 mg weekly arm
- Phase 3 TRIUMPH-4: 28.7 % mean body-weight reduction at 68 weeks — the largest reported for any approved or investigational anti-obesity peptide to date
- Phase 3 TRANSCEND-T2D-1 (Lancet, 2026): substantial HbA1c and body-weight reductions in type-2-diabetes subjects
Research dosing in the literature
Published research protocols dose retatrutide once weekly via subcutaneous administration, with stepwise escalation from 2 mg up to 12 mg over several weeks to minimize gastrointestinal effects observed in clinical work. Research vials are typically 10 mg lyophilized.
Storage
Lyophilized retatrutide is stable for 24+ months at −20 °C. Reconstituted vials should be refrigerated at 2–8 °C and used within 28 days.
FAQ
Is retatrutide FDA approved?
No. Retatrutide is investigational. Phase 3 results have been reported but it has not received marketing authorization.
How is retatrutide different from tirzepatide?
Tirzepatide activates two receptors (GIP, GLP-1). Retatrutide adds glucagon-receptor agonism, which increases resting energy expenditure and hepatic lipid mobilization.
What does 'GLP-3' actually mean?
It is informal industry shorthand for retatrutide as the third generation of the GLP-class metabolic peptides. There is no receptor named 'GLP-3'.