Retatrutide
LY3437943 · sold as “GLP-X3”
Investigational GIP / GLP-1 / glucagon triple agonist with the largest weight reductions reported in a phase 2 obesity trial.
Not FDA-approved. Phase 3 investigational drug. Not FDA- or EMA-approved. Compounded or ‘research’ versions are not regulated equivalents. This page describes research and public discussion; it is not a recommendation to use.
Overview
Retatrutide is a once-weekly injectable peptide developed by Eli Lilly that activates three hormone receptors involved in appetite and energy balance. In a 48-week phase 2 trial it produced mean weight loss of roughly 24% at the highest dose. Phase 3 (TRIUMPH) trials are ongoing; it is not approved anywhere.
Mechanism of action
Agonism at GLP-1 receptors (satiety, slowed gastric emptying, insulin secretion), GIP receptors (insulin secretion, possible adipose effects), and glucagon receptors (increased energy expenditure and hepatic fat oxidation).
Benefits & evidence ratings
Dosing
Doses show what has been studied or discussed — not guidance. Always follow your prescriber.
| Source | Dose | Frequency | Duration | Route |
|---|---|---|---|---|
Phase 2 obesity trial (Jastreboff 2023) B Human clinical data | 1, 4, 8 or 12 mg (with dose escalation from 2 mg for higher arms) | Once weekly | 48 weeks | Subcutaneous |
Online / compounded protocols D Anecdotal / community Not validated; product purity and dose accuracy are unverified. | Often start ~1–2 mg, titrated monthly | Weekly | Open-ended | Subcutaneous |
Clinical trials & studies
- Phase 22023Triple–Hormone-Receptor Agonist Retatrutide for Obesity — A Phase 2 Trial (NEJM)
338 adults; mean weight change at 48 wk of −24.2% at 12 mg vs −2.1% placebo.
- Phase 22023Retatrutide in type 2 diabetes — phase 2 trial (Lancet)
Dose-dependent HbA1c and weight reductions over 36 weeks.
- Phase 3OngoingTRIUMPH phase 3 program
Ongoing registered trials in obesity, OSA and knee osteoarthritis.
Safety
Side effects
- Nausea, vomiting, diarrhea, constipation (dose-related, mostly during escalation)
- Increased heart rate (dose-dependent, peaked ~24 wk in phase 2)
- Dysesthesia/skin sensitivity reported at higher doses
- Reduced appetite and possible lean-mass loss
Contraindications
- Pregnancy or planning pregnancy
- Personal/family history of medullary thyroid carcinoma or MEN2 (class concern for incretins)
- History of pancreatitis (caution)
Interactions
- Insulin or sulfonylureas — hypoglycemia risk
- Oral drugs with narrow therapeutic index — delayed gastric emptying may alter absorption
- Do not combine with other GLP-1 agonists
Long-term safety
Unknown beyond ~48 weeks of controlled exposure. Phase 3 outcome and safety data are pending.
Regulatory status
Investigational
Phase 3 investigational drug. Not FDA- or EMA-approved. Compounded or ‘research’ versions are not regulated equivalents.
FAQ
Commonly discussed alongside
Listing a combination does not mean it has been studied or is safe.
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