Retatrutide Peptide Profile
Overview:
Retatrutide (LY‑3437943) is a novel investigational peptide‑based drug developed by Eli Lilly and Company as a triple‑hormone receptor agonist targeting the glucagon‑like peptide‑1 (GLP‑1) receptor, the glucose‑dependent insulinotropic polypeptide (GIP) receptor, and the glucagon receptor (GCGR) to address obesity, type 2 diabetes (T2D), and related metabolic dysfunctions. Because it simultaneously engages all three receptors, it is often nicknamed “Triple G.” Retatrutide is currently undergoing Phase III clinical trials and has not received FDA approval for clinical use, though top‑line data indicate strong efficacy in weight loss and metabolic improvement. (Wikipedia)
Mechanism of Action:
Retatrutide’s integrated mechanism leverages the combined effects of three incretin/glucagon pathways:
• GLP‑1R agonism enhances glucose‑dependent insulin secretion, inhibits glucagon release, slows gastric emptying, and suppresses appetite. (Synapse)
• GIPR agonism further potentiates insulin release and may improve adipose tissue metabolism. (New England Journal of Medicine)
• GCGR agonism can increase energy expenditure and may promote fat oxidation beyond what GLP‑1/GIP co‑agonists achieve. (Synapse)
These combined effects contribute to appetite suppression, improved glycaemic control, enhanced fat loss, and reduced liver fat in clinical settings. (Nature)
Clinical Outcomes (Research Data):
In Phase II/III research, once‑weekly retatrutide injections produced substantial reductions in body weight — up to approximately 24 % body‑weight loss at 48 weeks and up to **~28.7 % at 68 weeks in osteoarthritis‑included populations — outperforming many current incretin therapies. (Nature)
It also demonstrated clinically meaningful improvements in glycaemic control for adults with T2D, and evidence suggests favourable effects on body composition and liver fat. (PubMed)
Safety & Regulatory Status:
Retatrutide is investigational and not FDA‑approved; its safety profile in trials echoes typical incretin therapy effects (e.g., gastrointestinal symptoms such as nausea, vomiting, and diarrhea). (Wikipedia) Use of unregulated or grey‑market products claiming to be retatrutide poses significant safety and legal risks. (The Verge)
Experimental/Clinical Dosing Chart (Investigational Trials):
| Dose Strength | Frequency | Route | Primary Population/Indication | Notes |
| 3 mg | Once weekly | Subcutaneous | Obesity/T2D | Early phase optimised doses in trials (Wikipedia)
| 6 mg | Once weekly | Subcutaneous | Obesity/T2D | Middle dose level in Phase II/III (Nature)
| 8 mg | Once weekly | Subcutaneous | Obesity | Higher trial dose showing up to ~22.8 % weight loss (Nature)
| 12 mg | Once weekly | Subcutaneous | Obesity/Knee OA cohort | Highest investigational dose; ~28.7 % weight reduction at 68 wk (PR Newswire)
References (APA):
Retatrutide. (2025). Wikipedia. https://en.wikipedia.org/wiki/Retatrutide (Wikipedia)
Jastreboff, A. M., et al. (2023). Triple–Hormone‑Receptor Agonist Retatrutide for Obesity. New England Journal of Medicine. (New England Journal of Medicine)
Retatrutide: What it is and how it works. (2025). Oviva. https://oviva.com/uk/en/retatrutide‑weight‑loss/ (Oviva Group)
Sanyal, A. J., et al. (2024). Triple agonist retatrutide study results. Nature Medicine. (Nature)
Retatrutide clinical data for T2D and body composition. (2025). PubMed. https://pubmed.ncbi.nlm.nih.gov/40609566/ (PubMed)
