Retatrutide
A first-in-class triple hormone receptor agonist (GLP-1/GIP/glucagon) that achieved up to 24.2% weight reduction in phase 2 clinical trials.
Retatrutide (LY3437943) is an investigational once-weekly injectable peptide developed by Eli Lilly that simultaneously activates three metabolic hormone receptors: GLP-1, GIP, and glucagon. In a landmark phase 2 trial published in the New England Journal of Medicine, the 12 mg dose achieved 24.2% mean body weight reduction at 48 weeks, with 100% of participants losing at least 5% of their body weight. It also demonstrated remarkable liver fat reduction of up to 82%.
⚙️ Mechanism of Action
Retatrutide simultaneously engages three receptor pathways: GLP-1 receptor activation reduces appetite and slows gastric emptying; GIP receptor activation enhances insulin secretion and may amplify GLP-1 effects on weight; glucagon receptor activation increases hepatic energy expenditure and fat oxidation. This triple agonism creates synergistic metabolic effects that exceed those of dual-agonist therapies, particularly in driving energy expenditure and reducing liver fat.
✅ Benefits
- •Up to 24.2% body weight reduction at 48 weeks in trials
- •Reduces liver fat by up to 82%
- •Improves HbA1c by up to 2.2% in type 2 diabetes
- •Once-weekly dosing convenience
- •Superior weight loss compared to dual-agonist approaches
- •100% of participants achieved clinically meaningful weight loss at highest dose
⚠️ Risks & Considerations
- •Nausea and vomiting (most common, usually transient)
- •Diarrhea and constipation
- •Decreased appetite
- •Injection site reactions
- •Potential gallbladder events (under investigation)
📚 References
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