Hormonal
Triple agonist retatrutide (GLP-1/GIP/glucagon) produces superior weight loss (up to 24.2% at 12mg) compared to dual agonists and GLP-1 monotherapy, driven by synergistic activation of all three receptors.
Retatrutide, a once-weekly injection targeting three gut hormones, has shown unprecedented weight loss (up to 24%) in clinical trials for obesity. While effective, it carries a risk of gastrointestinal side effects like nausea, which are usually manageable by starting at a low dose and increasing slowly. It represents a significant advancement over older GLP-1 drugs.
The 2023 phase 2 double-blind, randomized controlled trial evaluating a GLP-1/GIP/glucagon receptor triagonist (retatrutide) in patients with the disease of obesity reported 24.2% weight loss at 48 weeks with 12 mg retatrutide.
Why this rating
Based on a Phase 2 RCT, which is high quality but not yet Phase 3 results.
Source
The Road towards Triple Agonists: Glucagon-Like Peptide 1, Glucose-Dependent Insulinotropic Polypeptide and Glucagon Receptor - An Update
Agnieszka Jakubowska et al. · Endocrinology and Metabolism · 2024
DOI 10.3803/enm.2024.1942
More from this paper
- Glucagon receptor activation in triple agonists increases energy expenditure and lipid oxidation, contributing to weight loss without causing hyperglycemia when combined with GLP-1 and GIP.Good
- Triple agonists (retatrutide, SAR441255) demonstrate superior efficacy in reversing fatty liver disease (MASH) compared to dual agonists and GLP-1 monotherapy.Moderate
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