Retatrutide: The Triple-Agonist
Revolutionizing Weight Loss
Eli Lilly's LY3437943 delivered -28.7% body weight reduction in Phase 3 trials — the largest mean weight loss ever recorded in a randomized obesity trial. Here's the complete clinical breakdown.
All content is for educational and research purposes only. Peptides discussed are research compounds not approved by the FDA for human use. Nothing on this page constitutes medical advice.
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Retatrutide at a Glance
-28.7%
Phase 3 Weight Loss
TRIUMPH-4, 68 wks, 12mg
-24.2%
Phase 2 Weight Loss
NEJM 2023, 48 wks, 12mg
-82.4%
Liver Fat Reduction
Nature Medicine 2024
71.2 lbs
Avg Absolute Loss
TRIUMPH-4, 12mg
What Makes Retatrutide Different
Triple GIP/GLP-1/Glucagon receptor agonist — the only one in its class
GLP-1 Receptor
Appetite suppression via hypothalamic satiety centers. Same target as Ozempic/Wegovy.
GIP Receptor
Enhanced insulin sensitivity and fat metabolism. Shared with Tirzepatide.
Glucagon Receptor
Thermogenesis, hepatic fat oxidation, energy expenditure. Unique to Retatrutide.
The glucagon component contributes an estimated additional 2–3% body weight loss beyond dual agonism through thermogenesis and hepatic fat mobilization — compounding across 68+ week treatment periods.
Retatrutide vs Semaglutide vs Tirzepatide
| Feature | Semaglutide | Tirzepatide | Retatrutide ★ |
|---|---|---|---|
| Receptors | GLP-1 only | GLP-1 + GIP | GLP-1 + GIP + Glucagon |
| Max Weight Loss | -14.9% | -22.5% | -28.7% |
| Key Trial | STEP 1 (NEJM) | SURMOUNT-1 | TRIUMPH-4 Phase 3 |
| Liver Fat Reduction | Limited data | ~50% | -82.4% |
| FDA Status | Approved (Wegovy) | Approved (Zepbound) | Phase 3 |
| GI Discontinuation | 5.6% | 2.7% | 18.2% |
Phase 2 Trial Results
338 participants · 48 weeks · DOI: 10.1056/NEJMoa2301972
| Dose | 24 Weeks | 48 Weeks | ≥5% Loss | ≥15% Loss |
|---|---|---|---|---|
| Placebo | -1.6% | -2.1% | 27% | 2% |
| 4 mg | -12.9% | -17.1% | 92% | 60% |
| 8 mg | -17.3% | -22.8% | 100% | 75% |
| 12 mg ★ | -17.5% | -24.2% | 100% | 83% |
Clav's Primary Peptide — Clav Tides
GLP-3 R 15mg
Shop Retatrutide
Research-grade GLP-3 R (Retatrutide) — >98% purity, COA included, multiple vial sizes.
TRIUMPH-4 Phase 3 Results
445 participants · 68 weeks · December 2025
-28.7%
12mg Weight Loss
68 weeks
-26.4%
9mg Weight Loss
68 weeks
71.2 lbs
Average Absolute Loss
12mg dose
-14.0 mmHg
Systolic BP Reduction
12mg dose
The TRIUMPH-4 results represent the largest mean weight loss ever recorded in a randomized, placebo-controlled obesity trial for any pharmacotherapy. The 5,800+ participant TRIUMPH program has seven additional Phase 3 readouts expected throughout 2026.
Liver Fat Reduction: -82.4%
Phase 2a sub-study · Nature Medicine 2024 · 24 weeks
| Dose | Liver Fat Change (24 wks) |
|---|---|
| Placebo | +0.3% |
| 1 mg | -42.9% |
| 4 mg | -57.0% |
| 8 mg | -81.4% |
| 12 mg ★ | -82.4% (p < 0.001) |
Among the largest liver fat reductions ever documented with any pharmacotherapy. For reference, dedicated MASLD drugs like resmetirom typically achieve 30–50% reductions. The glucagon receptor component directly drives hepatic lipid mobilization — even the 1mg dose achieved -42.9%, partially independent of systemic weight loss.
Safety & Side Effects
Higher Discontinuation Rate
Retatrutide showed an 18.2% adverse-event discontinuation rate at 12mg (TRIUMPH-4), vs 5.6% for semaglutide and 2.7% for tirzepatide. More receptors = more metabolic disruption. The 9mg dose (12.2% discontinuation, -26.4% weight loss) may be a better balance point.
| Side Effect | Incidence (8–12mg) |
|---|---|
| Nausea | 38–43% |
| Diarrhea | 33–35% |
| Constipation | 22–25% |
| Vomiting | 20–21% |
| Decreased Appetite | 18–19% |
Retatrutide at Clav Tides
Frequently Asked Questions
What is retatrutide and how does it work?
Retatrutide (LY3437943) is a first-in-class triple GIP/GLP-1/Glucagon receptor agonist by Eli Lilly. It simultaneously activates GIP (insulin sensitivity), GLP-1 (appetite suppression), and glucagon (thermogenesis, hepatic fat oxidation) receptors — the first compound to do all three.
How much weight loss does retatrutide produce?
Phase 2 (NEJM 2023, n=338): -24.2% at 12mg over 48 weeks. Phase 3 TRIUMPH-4 (Dec 2025, n=445): -28.7% at 12mg over 68 weeks, averaging 71.2 lbs per participant — the highest ever recorded in a randomized obesity trial.
How does retatrutide compare to semaglutide and tirzepatide?
Retatrutide: -28.7%. Tirzepatide: -22.5%. Semaglutide: -14.9%. The glucagon receptor component adds thermogenesis and hepatic fat oxidation that neither competitor has. The tradeoff is higher GI side effects (18.2% discontinuation vs 2.7% tirzepatide).
Is retatrutide FDA-approved?
No. As of March 2026, retatrutide is in Phase 3 trials. The TRIUMPH program has 5,800+ participants across multiple trials. Earliest possible approval: 2027-2028. Available as research-grade peptide only.
What are the most common side effects?
Nausea (38-43%), diarrhea (33-35%), constipation (22-25%), vomiting (20-21%). Most are transient, peaking during dose escalation. Slower titration (starting at 2mg) substantially reduces incidence. The 9mg dose offers a better tolerability profile at -26.4% weight loss.
Research Retatrutide Today
GLP-3 R (Retatrutide) from Clav Tides — >98% purity, COA documentation, multiple vial sizes.
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