In plain English
Retatrutide is a newer weight-loss peptide that acts on three hormone receptors at once: GLP-1 and GIP (like tirzepatide) plus glucagon. It lowers appetite and also appears to increase the energy your body burns. In large studies it produced more weight loss than any other peptide in its class.
What it's used for
- Weight loss, with or without type 2 diabetes
- Weight loss with knee osteoarthritis pain
- Weight loss with obstructive sleep apnea
- Weight loss in people with heart disease
- Also being studied for fatty liver disease and kidney disease
Benefits
In human studies, retatrutide has shown:
- About 24% average weight loss over 48 weeks at 12 mg weekly (phase 2, NEJM 2023)
- About 21% average weight loss over 80 weeks at 12 mg in people with type 2 diabetes, with HbA1c drops of 1.4–1.6 points (TRIUMPH-2)
- About 22–23% average weight loss over 80 weeks in people with severe obesity and heart disease (TRIUMPH-3)
- Average weight loss of up to about 71 lb, with less knee pain, in people with knee osteoarthritis
- Strong appetite control plus higher energy use
How it works
In simple terms: retatrutide turns down appetite like other GLP-1 medicines and also turns up energy use.
It activates three receptors. GLP-1 and GIP activity reduce hunger, slow stomach emptying and improve insulin release, as with tirzepatide. The third target, the glucagon receptor, is unusual for a weight-loss drug: glucagon normally raises blood sugar, but in this balanced combination it appears to increase energy expenditure and fat burning in the liver, while the GLP-1 and GIP effects keep blood sugar in check. A fatty-acid side chain gives it a long half-life for once-weekly dosing.
Development history
Developed by Eli Lilly as the successor to tirzepatide.
- 2023: Phase 2 results published in the New England Journal of Medicine.
- Late 2025–2026: A series of large phase 3 TRIUMPH studies report strong weight-loss results, including in people with type 2 diabetes, heart disease, knee osteoarthritis and sleep apnea.
Typical protocols
In Lilly’s clinical studies, retatrutide was given once weekly with a gradual step-up:
| Study | Dosing | Length |
|---|---|---|
| Phase 3 (TRIUMPH) | Started at 2 mg weekly, stepped up gradually to 4, 9 or 12 mg weekly | 68–80 weeks |
| Phase 2 | Target doses of 1, 4, 8 or 12 mg weekly, reached by step-up from 2 mg (some groups from 4 mg) | 48 weeks |
Users report following a similar slow step-up, often starting at 1–2 mg weekly and increasing every 4 weeks as tolerated. Doses are in milligrams, so double-check mg versus mcg and your syringe reading; the calculator below does the conversion.
Cycling
Retatrutide was given continuously in studies. As with other GLP-1 type peptides, appetite and weight tend to return after stopping.
Administration options
Subcutaneous injection once a week, on the same day each week, in the belly, thigh or upper arm.
Reconstitution and dosing calculator
Retatrutide is commonly sold in 10–30 mg vials. Check the vial strength carefully before mixing, since doses are in milligrams.
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This tool does arithmetic only. It does not choose a dose or confirm that any substance is right for you. Double-check every result against your syringe and your clinician’s instructions.
Side effects and safety
- Most common in studies: diarrhea, nausea, constipation, lower appetite and vomiting, mostly mild to moderate and most frequent while the dose is being raised.
- In TRIUMPH-3, diarrhea occurred in about 24–30% of people on retatrutide versus about 9% on placebo, and about 13.5% stopped the 12 mg dose because of side effects.
- Resting heart rate rose slightly in earlier studies, more so at higher doses.
- Shared GLP-1 class cautions: pancreatitis, gallbladder problems and dehydration; people with a personal or family history of medullary thyroid cancer or MEN 2 syndrome are generally advised to avoid this class.
- Long-term effects beyond about 80 weeks are still being studied.
Common stacks
- Not combined with semaglutide, tirzepatide or other GLP-1 peptides.
- Users report pairing it with growth hormone peptides or BPC-157, but these combinations have not been studied.
Storage
Powder: keep cold, dry and away from light.
After mixing with bacteriostatic water: refrigerate at 2–8 °C and protect from light.
Compare with
- Tirzepatide: dual agonist (GLP-1 and GIP); retatrutide adds glucagon and showed more weight loss in studies.
- Semaglutide: GLP-1 only, with proven heart-risk reduction.
- Survodutide and mazdutide: newer dual GLP-1/glucagon peptides.
Frequently asked questions
Is "GLP-3" the same as retatrutide?
“GLP-3” is a nickname some sellers use. There is no GLP-3 hormone; retatrutide acts on GLP-1, GIP and glucagon receptors.
How does it compare with tirzepatide?
Average weight loss has been higher with retatrutide in studies, though the two have not been compared head to head in a large published study.
What dose do people start at?
Studies started at 2 mg weekly. Users report starting at 1–2 mg and stepping up slowly to limit nausea.
How fast does it work?
Appetite usually drops within the first weeks; most weight loss builds over many months as the dose is raised.
References
- Jastreboff AM, et al. Triple-hormone-receptor agonist retatrutide for obesity — a phase 2 trial. N Engl J Med. 2023;389:514-526.
- HCPLive. Retatrutide meets phase 3 weight loss endpoints in 2 obesity trials (July 23, 2026). https://www.hcplive.com/view/retatrutide-meets-phase-3-weight-loss-endpoints-in-2-obesity-trials
- Drugs.com. Retatrutide development history. https://www.drugs.com/history/retatrutide