What is Retatrutide?
Retatrutide (development code LY3437943, commonly shortened to Reta in research discussions) is an investigational single-molecule peptide from Eli Lilly that activates three receptors at once: GLP-1 (glucagon-like peptide-1), GIP (glucose-dependent insulinotropic polypeptide) and the glucagon receptor. That makes it the first “triagonist” to reach late-stage obesity trials.
The simplest way to place it is on a one-two-three ladder of incretin agonists. Semaglutide hits one receptor (GLP-1). Tirzepatide hits two (GIP + GLP-1). Retatrutide hits three by adding glucagon-receptor agonism. Each added pathway has, so far, tracked with a larger reported weight-loss signal in the respective trials.
Unlike semaglutide and tirzepatide, retatrutide is not yet approved anywhere. It is still in clinical development. Everything below is published research data, supplied here for laboratory research context only.
Effects, what does the research say?
Phase 2, the first obesity signal
The Phase 2 obesity trial (Jastreboff et al., 2023, n=338) was the result that put retatrutide on the map:
- Mean weight change of about −24% at the 12 mg weekly dose over 48 weeks, vs −2% for placebo
- Dose-dependent response across 1 mg, 4 mg, 8 mg and 12 mg arms
- Weight loss had not clearly plateaued by week 48 at the higher doses
- Gastrointestinal events (nausea, diarrhoea) were the dominant adverse-event class, consistent with the rest of the incretin field
“In this 48-week phase 2 trial, treatment with retatrutide resulted in substantial reductions in body weight in adults with obesity.”
Jastreboff AM et al. (2023), Triple-Hormone-Receptor Agonist Retatrutide for Obesity (Phase 2). New England Journal of Medicine. · PMID 37366315 ↗
Phase 3, TRIUMPH-1 topline (2026)
Eli Lilly reported topline results from TRIUMPH-1, the pivotal Phase 3 obesity trial, in May 2026 (n=2,339 adults with obesity or overweight plus a weight-related condition, without type 2 diabetes):
- Mean weight reduction at 80 weeks: 19.0% (4 mg), 25.9% (9 mg) and 28.3% (12 mg)
- 45.3% of participants on 12 mg achieved ≥30% weight loss
- In an extended-follow-up subgroup (starting BMI ≥35), continued treatment reached up to 30.3% mean reduction at 104 weeks
- Most common adverse events at 12 mg: nausea (~42%), diarrhoea (~32%), constipation (~26%), vomiting (~25%), mostly during escalation
“Retatrutide delivered weight loss approaching levels historically associated only with bariatric surgery in its pivotal Phase 3 obesity trial.”
Eli Lilly, TRIUMPH-1 Phase 3 topline results, May 2026. · Lilly topline ↗
The one-two-three ladder, how the three compare
Comparing trial programmes (not head-to-head, and across different durations and populations), the reported mean weight reduction rises with each added receptor:
| Compound | Receptors | Reported weight loss | Status |
|---|---|---|---|
| Semaglutide | GLP-1 (single) | ~15% (STEP trials) | Approved |
| Tirzepatide | GIP + GLP-1 (dual) | ~21% (SURMOUNT trials) | Approved |
| Retatrutide | GIP + GLP-1 + glucagon (triple) | ~28-30% (TRIUMPH-1) | Investigational |
Why the glucagon receptor matters
The three receptors do different jobs, and stacking them is the whole idea:
- GLP-1: reduces appetite and slows gastric emptying (the appetite lever)
- GIP: modulates insulin response and fat-tissue handling, and may blunt GLP-1-driven nausea
- Glucagon: raises basal energy expenditure and supports hepatic fat mobilisation (the “burn” lever, not just the “eat-less” lever)
Adding the glucagon arm is the leading explanation for why retatrutide's reported weight loss runs ahead of dual GIP/GLP-1 agonists at matched durations. It also draws extra research interest in hepatic-fat (NAFLD/MASLD) end-points.
Dosage, what is being researched?
Important: Retatrutide is investigational and not approved. The figures below reflect published Phase 2/Phase 3 protocols and are provided for research context only, not a dosing recommendation.
| Setting | Starting Dose | Studied Maintenance | Escalation |
|---|---|---|---|
| Phase 3 (TRIUMPH) | 2 mg/week | 4 / 9 / 12 mg/week | Gradual, monthly steps |
| Phase 2 (obesity) | 2-4 mg/week | up to 12 mg/week | Gradual titration |
| Research protocols | 2 mg/week | Per study design | Slow ramp to limit GI events |
Storage & Reconstitution
- Lyophilised powder: Refrigerator (2-8°C), protected from light, long-term storage.
- After reconstitution with bacteriostatic water: refrigerated, use within ~28 days.
- Do not freeze the reconstituted solution. Add water slowly along the glass wall, do not shake, swirl gently.
- Verify quality: insist on a CoA with HPLC purity, LC-MS identity (lipidated mass) and ICP-MS heavy metals.