Retatrutide is the compound that rewrote what people thought was possible in metabolic science. It is a once-weekly injectable that activates three metabolic receptors at once (GLP-1, GIP, and glucagon), and in clinical trials it has produced the largest body-weight reductions ever recorded for its class. That third receptor is the reason, and it is what sets retatrutide apart from every GLP-1 compound that came before it.
What retatrutide is
Retatrutide (originally coded LY3437943, developed by Eli Lilly) is a triple agonist. Most of the well-known metabolic compounds target one receptor or two. Retatrutide adds a third, the glucagon receptor, on top of GLP-1 and GIP. Each receptor pulls a different lever in metabolism, and engaging all three together is what drives its results.
What the research shows
The trial that put retatrutide on the map was published by Jastreboff and colleagues in the New England Journal of Medicine in 2023. Across 338 adults with obesity over 48 weeks, the results were remarkable. Participants on the 12 mg dose lost an average of 24.2% of their body weight, and the 8 mg dose produced 22.8%. Every participant on the 8 mg and higher doses lost at least 5% of their body weight, and the majority crossed the 15% mark. The accompanying NEJM editorial described the efficacy as unprecedented.
The benefits reached well past the scale. A 2024 substudy in Nature Medicine by Sanyal and colleagues looked at participants with high liver fat and reported reductions of roughly 81 to 82% at the higher doses, with most participants returning to normal liver fat levels. A separate phase 2 trial in The Lancet (Rosenstock and colleagues, 2023) showed strong results in people with type 2 diabetes, with major improvements in blood sugar control alongside the weight loss.
How it works
The three receptors each do something useful, and together they add up. GLP-1 reduces appetite and slows how quickly the stomach empties, so fullness comes sooner and lasts longer. GIP supports the body’s insulin response and appears to improve how it handles fat. The glucagon receptor, the new addition, increases energy expenditure, meaning the body burns more, and it is a major driver of the dramatic liver-fat reductions seen in the trials. Engaging all three at once is what produces the combined effect that no single or dual agonist has matched.
Quick facts
| Retatrutide | |
|---|---|
| Type | Triple receptor agonist (GLP-1, GIP, glucagon) |
| Developed by | Eli Lilly (LY3437943) |
| Best known for | The largest weight-loss results in its class |
| Trial result | Average 24.2% weight loss at 48 weeks (12 mg) |
| Also shown | ~81-82% liver fat reduction; improved blood sugar |
| Dosing studied | Once weekly, subcutaneous |
| Form | Lyophilized powder, reconstituted before use |
What to look for when buying
With a compound this potent, purity is everything, so the testing behind a batch matters as much as the peptide itself. Look for a Certificate of Analysis (COA) from third-party testing and an HPLC-MS purity figure of 99% or higher. Every batch of Marek Pharma’s retatrutide is HPLC-MS tested with a COA, lyophilized for stability, and ships from within Canada.
References
- Jastreboff AM, Kaplan LM, Frías JP, et al. Triple-Hormone-Receptor Agonist Retatrutide for Obesity, A Phase 2 Trial. New England Journal of Medicine, 2023;389(6):514-526.
- Sanyal AJ, Kaplan LM, Frías JP, et al. Triple hormone receptor agonist retatrutide for metabolic dysfunction-associated steatotic liver disease, a randomized phase 2a trial. Nature Medicine, 2024.
- Rosenstock J, Frías JP, Jastreboff AM, et al. Retatrutide, a GIP, GLP-1 and glucagon receptor agonist, for people with type 2 diabetes, a phase 2 trial. The Lancet, 2023;402(10401):529-544.
For laboratory and research use only.