Retatrutide GLP-1 GIP Glucagon Triple Agonist

Overview

Retatrutide (a.k.a. GLP-3):

is a metabolic peptide developed by Eli Lilly that acts as a triple receptor agonist, targeting GLP-1, GIP, and glucagon receptors. It's currently being studied for obesity and metabolic disease due to its effects on appetite regulation, energy expenditure, and glucose metabolism.

Unlike earlier GLP-1's that primarily focus on appetite suppression, retatrutide’s additional glucagon receptor may influence energy expenditure and fat metabolism, which is part of why it's drawn significant interest in metabolic research.

Mechanism of Action:
Retatrutide activates three pathways involved in metabolic regulation:

1. GLP-1 receptor agonism

   • Appetite suppression

   • Slower gastric emptying

   • Improved insulin secretion

2. GIP receptor agonism

   • Modulation of insulin release

   • Potential improvements in metabolic efficiency

3. Glucagon receptor agonism

   • Increased energy expenditure

   • Potential influence on fat metabolism and liver energy balance

The combination across these pathways is why it’s often described as a "triple agonist” therapy.

Sources:

Phase 2 Clinical Trial (PubMed)
https://pubmed.ncbi.nlm.nih.gov/37366315/

New England Journal of Medicine Publication
https://www.nejm.org/doi/full/10.1056/NEJMoa2301972

ClinicalTrials.gov (example ongoing study)
https://clinicaltrials.gov/study/NCT05882045

Eli Lilly trial announcement and overview
https://investor.lilly.com/news-releases/news-release-details/lillys-phase-2-retatrutide-results-published-new-england-journal