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.
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 — Apollo Peptide Sciences
GLP-3 R 15mg
Shop Retatrutide from Apollo
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 Apollo Peptide Sciences
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 Apollo Peptide Sciences — >98% purity, COA documentation, multiple vial sizes.