Retatrutide
Retatrutide is an investigational once-weekly injectable triple agonist activating GLP-1, GIP, and glucagon receptors, currently in Phase 3 (TRIUMPH program) obesity trials after producing the largest average weight loss (~24% in Phase 2, up to ~30% in Phase 3 extension) reported for an incretin therapy to date. It is not FDA-approved and is not available as a prescription drug anywhere.
Retatrutide reconstitution calculator
Open full calculator →Typical dosing
| Goal | Range | Route | Frequency |
|---|---|---|---|
| Obesity, no type 2 diabetes (Phase 2, NEJM 2023) | 1, 4, 8, or 12 mg (trial arms) | SubQ weekly | 48 weeks, with 12-week dose-escalation to improve tolerability |
| Obesity with weight-related comorbidity (Phase 3 TRIUMPH-1) | 4, 9, or 12 mg (trial arms) | SubQ weekly | 80 weeks primary endpoint; extension data to 104 weeks |
| Obesity + knee osteoarthritis (Phase 3 TRIUMPH-4) | up to 12 mg (trial arm) | SubQ weekly | 68 weeks |
| Liver fat / MASLD (Phase 2a, Nature Medicine) | up to 12 mg (trial arms) | SubQ weekly | 24 weeks |
| Obesity + type 2 diabetes (Phase 3 TRIUMPH-2) | not yet publicly reported by dose | SubQ weekly | trial ongoing, results not yet published |
Ranges compiled from research literature — not a prescription.
How it works
Retatrutide is a single-molecule peptide, 39 amino acids, engineered to simultaneously activate three receptors: the glucagon-like peptide-1 receptor (GLP-1R), the glucose-dependent insulinotropic polypeptide receptor (GIPR), and the glucagon receptor (GCGR). A C20 fatty-acid side chain lets it bind albumin non-covalently, extending its half-life to roughly six days and enabling once-weekly dosing, similar in concept to tirzepatide's fatty-acid conjugation but with glucagon receptor activity added on top.
The rationale for adding glucagon-receptor agonism to the GLP-1/GIP combination already used by tirzepatide is that glucagon receptor activation increases energy expenditure and hepatic fat oxidation, which is proposed to add a thermogenic, calorie-burning effect on top of the appetite suppression and delayed gastric emptying produced by GLP-1/GIP agonism. This is why retatrutide is sometimes called a 'triple-G' or 'GGG' agonist in the literature.
The evidence base is still limited to clinical trials, not real-world prescribing. In the Phase 2 trial published in the New England Journal of Medicine (Jastreboff et al., 2023), 338 adults with obesity or overweight without type 2 diabetes received weekly subcutaneous retatrutide (1, 4, 8, or 12 mg) or placebo for 48 weeks; the 12 mg group lost a mean of about 24.2% of body weight, exceeding results reported at the time for semaglutide 2.4 mg (~15% at 68 weeks) and tirzepatide 15 mg (~22.5% at 72 weeks). A separate Phase 2a trial in metabolic dysfunction-associated steatotic liver disease (MASLD), published in Nature Medicine, reported substantial reductions in liver fat content. Eli Lilly's Phase 3 TRIUMPH-1 trial (obesity with a weight-related comorbidity) later reported average weight loss of up to 30.3% (about 85 lbs) at 104 weeks in a pre-specified extension for participants with BMI >=35, and TRIUMPH-4 (obesity plus knee osteoarthritis) reported ~28.7% weight loss alongside meaningful reductions in WOMAC pain scores at 68 weeks.
Despite these results, retatrutide remains investigational: it has not completed Phase 3, has not been submitted for or granted FDA approval, and no long-term safety or outcomes data beyond the trial periods exist. It is nonetheless sold on the 'research chemical' grey market, produced outside FDA oversight and typically labeled 'not for human consumption,' where independent testing has found meaningful rates of contamination, incorrect peptide sequences, and endotoxin levels above safety thresholds.
Side effects & safety
- Gastrointestinal side effects (nausea, vomiting, diarrhea) are the most common adverse events across all published trials and tend to increase with dose, consistent with the wider GLP-1 receptor agonist class.
- Retatrutide is investigational — no long-term (multi-year) safety, cardiovascular outcome, or real-world data exist yet outside the ongoing trial population.
- It is not FDA-approved for any indication; it cannot legally be prescribed or dispensed as a medicine in the United States or elsewhere at this time.
- Grey-market vials sold as 'research chemical' or 'not for human consumption' are not FDA-reviewed for identity, strength, purity, or sterility — independent testing of similar grey-market peptides has found high rates of endotoxin contamination and incorrect sequences.
- Dose-escalation protocols used in trials (gradual titration over roughly 12 weeks) were specifically designed to improve tolerability; ad hoc, unsupervised dosing carries higher risk of adverse effects.
- Anyone considering retatrutide, in a trial or otherwise, should consult a licensed clinician; this is not a substitute for medical advice, and self-sourced investigational compounds carry risks that clinical-trial material does not.
Research
Primary sources — PubMed.
- Jastreboff AM, et al. Triple-Hormone-Receptor Agonist Retatrutide for Obesity — A Phase 2 Trial. N Engl J Med. 2023. https://www.nejm.org/doi/full/10.1056/NEJMoa2301972
- Loomba R, et al. Triple hormone receptor agonist retatrutide for metabolic dysfunction-associated steatotic liver disease: a randomized phase 2a trial. Nat Med. 2024. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11271400/
- Eli Lilly and Company. Lilly's triple agonist, retatrutide, delivered powerful weight loss in pivotal Phase 3 obesity trial (TRIUMPH-1). https://investor.lilly.com/news-releases/news-release-details/lillys-triple-agonist-retatrutide-delivered-powerful-weight-loss
- AJMC. Retatrutide Achieves Up to 30.3% Average Weight Loss in Phase 3 TRIUMPH-1 Trial. https://www.ajmc.com/view/retatrutide-achieves-up-to-30-3-average-weight-loss-in-phase-3-triumph-1-trial
- ClinicalTrials.gov. A Study of Retatrutide (LY3437943) on Renal Function in Participants With Overweight or Obesity and Chronic Kidney Disease. NCT05936151. https://clinicaltrials.gov/study/NCT05936151
- MedChemExpress. Retatrutide (LY3437943) Product Data Sheet — CAS 2381089-83-2, molecular formula C221H342N46O68, MW 4731.33. https://www.medchemexpress.com/retatrutide.html