Retatrutide
Also known as LY3437943, Triple G, GGG tri-agonist
Retatrutide is a once-weekly peptide that activates GLP-1, GIP and glucagon receptors together. Phase 2 data showed about 24 percent weight loss at 48 weeks, the largest figure reported for any single compound, but it is still years from approval.
Overview
Retatrutide is Eli Lilly's follow-up to tirzepatide: a single peptide that activates three receptors, GLP-1, GIP and glucagon. The glucagon component is the new piece. Glucagon receptor activation raises energy expenditure and pushes the liver to burn fat, which in theory adds a calories-out lever to the appetite lever that GLP-1 drugs already pull. It is a lipidated peptide dosed once weekly, same as its predecessors.
The Phase 2 obesity trial published in 2023 is why everyone is paying attention. At the 12 mg weekly dose, participants lost an average of about 24 percent of body weight at 48 weeks, and the curves had not flattened when the trial ended. A liver fat substudy showed most participants on the higher doses reaching normal liver fat. A separate Phase 2 in type 2 diabetes produced strong HbA1c reductions on top of the weight loss.
Phase 3 (the TRIUMPH program) is ongoing. Lilly reported topline results from one of those trials in late 2025 showing weight loss in the high 20s percent range at 68 weeks, but that came from a press release, not a peer-reviewed paper. There is no approved product anywhere, so everything sold as retatrutide is grey-market material of unverified purity, and the hype around it has attracted plenty of low-quality product.
How it works
Three receptors, three jobs. GLP-1 activation lowers appetite, slows gastric emptying and improves glucose-dependent insulin secretion. GIP activation adds to appetite suppression, may improve fat tissue metabolism and appears to reduce nausea. Glucagon receptor activation is the distinctive part: it increases resting energy expenditure, drives fat oxidation in the liver and lowers liver fat. On its own, glucagon would raise blood glucose, but the two incretin components offset that. Retatrutide is deliberately a weak GLP-1 agonist molecule for molecule and a stronger GIP and glucagon agonist, a balance chosen so that the metabolic effects come through without hyperglycemia.
What the research shows
- human RCT12 mg weekly produced about 24 percent mean weight loss at 48 weeks in adults with obesity, with loss still ongoing at trial end (Phase 2).
- human RCTOver 80 percent of participants with fatty liver on the higher doses reached normal liver fat by week 48 (Phase 2 substudy).
- human RCTLowered HbA1c by up to about 2 percentage points in type 2 diabetes alongside roughly 17 percent weight loss at the top dose (Phase 2).
- human RCTSponsor-reported Phase 3 topline results in late 2025 exceeded the Phase 2 figures; full peer-reviewed data still pending.
- human RCTHeart rate rose by several beats per minute early in treatment and drifted back toward baseline over time.
Evidence labels: rodent and in vitro mean no human data for that finding. Human pilot means small, often uncontrolled. Human RCT means randomized and controlled. Clinical means an approved drug with regulatory data.
Dose calculator
U-100 insulin syringeUnits are a volume on the syringe, not an amount of peptide. Concentration changes every time you change the water volume. The standalone calculator explains the math.
Dosing and protocol
Trials started at 1 or 2 mg weekly and increased every 4 weeks toward 4, 8 or 12 mg. Community users who copy the trial schedule usually hold at the lowest dose that controls appetite; 12 mg is not needed to get results.
Ongoing in trials. No withdrawal data yet, but weight regain after stopping should be assumed, as with every other GLP-1 class drug.
Same day each week, any time. Rotate injection sites.
| Vial | Suggested water | Concentration | Low dose draw |
|---|---|---|---|
| 10 mg | 1 mL | 10 mg/mL | 10 units |
| 20 mg | 2 mL | 10 mg/mL | 10 units |
| 30 mg | 3 mL | 10 mg/mL | 10 units |
Lyophilized: fridge 2-8C away from light, freezer for long-term. Reconstituted: fridge 2-8C, use within 4 weeks.
Cautions
- ▲Same GI side effects as the rest of the class, and the glucagon component can make early weeks rougher. Fast escalation was the main driver of dropouts in Phase 2.
- ▲Heart rate increases were larger than with semaglutide. People with arrhythmias or uncontrolled blood pressure should be careful.
- ▲A minority of Phase 2 participants reported skin tingling or heightened sensitivity (dysesthesia), which usually resolved.
- ▲No approved product exists, so every vial is unverified. Purity, concentration and even identity vary between suppliers.
- ▲Assume the class thyroid, pancreatitis and gallbladder warnings apply.
Frequently asked
Is retatrutide better than tirzepatide?
The Phase 2 weight loss numbers were larger, about 24 percent at 48 weeks versus around 20 percent for tirzepatide at 72 weeks, and the liver fat data are striking. But there has been no head-to-head trial, the Phase 3 data are not published, and tirzepatide has years of real-world safety behind it. On paper, yes; in practice, unproven.
When will it be approved?
Phase 3 trials run through 2026 and beyond. Even if everything goes well, an FDA decision is likely in 2027 at the earliest, with launch some time after that.
Why add glucagon to a weight loss drug?
Glucagon raises energy expenditure and burns liver fat, which are effects GLP-1 alone does not produce. It would normally raise blood sugar, but the GLP-1 and GIP activity cancel that out. The result is a drug that both cuts intake and raises output.
What dose are people actually using?
Most community protocols start at 1 to 2 mg weekly and hold at 4 to 8 mg. The 12 mg trial dose is rarely necessary and comes with more side effects. Because it is grey-market, the label dose and the actual dose are not always the same thing.
References
- Triple-hormone-receptor agonist retatrutide for obesity, a phase 2 trial. New England Journal of Medicine, 2023
- Retatrutide, a GIP, GLP-1 and glucagon receptor agonist, for people with type 2 diabetes: a randomised, double-blind, placebo and active-controlled, parallel-group, phase 2 trial. The Lancet, 2023
- Triple hormone receptor agonist retatrutide for metabolic dysfunction-associated steatotic liver disease: a randomized phase 2a trial. Nature Medicine, 2024
- LY3437943, a novel triple glucagon, GIP, and GLP-1 receptor agonist for glycemic control and weight loss: from discovery to clinical proof of concept. Cell Metabolism, 2022