Retatrutide
The Triple Agonist Revolution
Retatrutide is the world's first triple hormone agonist, targeting GLP-1, GIP, and Glucagon receptors. With up to 28.7% weight loss in Phase 3 trials, it may become the most powerful obesity treatment ever developed.
What Is Retatrutide?
Retatrutide (development code LY3437943) is Eli Lilly's investigational triple hormone receptor agonist. Unlike tirzepatide (Mounjaro/Zepbound) which targets two receptors, Retatrutide activates three: GLP-1, GIP, and Glucagon receptors.
Why glucagon? Adding glucagon receptor activation increases energy expenditure (calorie burning) and promotes fat breakdown in the liver. This third mechanism may explain the superior weight loss results compared to dual agonists.
Administration: Once-weekly subcutaneous injection, similar to Mounjaro and other GLP-1 medications.
The Triple Mechanism
GLP-1 Agonism
GIP Agonism
Glucagon Agonism
- • Increases energy expenditure
- • Promotes fat burning
- • Reduces liver fat
- • Unique to Retatrutide
Why This Matters
Most weight loss drugs only reduce calorie intake. Retatrutide's glucagon component also increases calorie burning, attacking obesity from both sides. This dual approach—eat less AND burn more—may explain the unprecedented weight loss results.
Phase 3 TRIUMPH-4 Results
BREAKING (December 2025): Recent topline results from the Phase 3 TRIUMPH-4 trial show Retatrutide delivers unprecedented weight loss and pain relief in patients with obesity and knee osteoarthritis.
At the 12mg dose, participants lost an average of 28.7% of their body weight (approx. 71.2 lbs) over 68 weeks. This significantly outperforms Phase 2 results.
Retatrutide reduced WOMAC pain scores by approximately 75% (4.5 points), offering substantial relief for osteoarthritis patients. 1 in 8 patients were completely pain-free.
Nearly 60% of participants on the 12mg dose lost at least 25% of their body weight. Remarkably, 23.7% of patients lost more than 35% of their weight.
Note: Seven additional Phase 3 trials are expected to complete in 2026, targeting obesity and diabetes.
Beyond Weight Loss
Liver Fat Reduction
Retatrutide showed remarkable effects on fatty liver disease (MASLD/MASH). In trials, participants achieved up to 86% reduction in liver fat content.
This positions Retatrutide as a potential treatment for MASH—a condition affecting millions with no currently approved medications.
Metabolic Improvements
- • Significant HbA1c reduction in diabetics
- • Improved blood pressure
- • Better lipid profiles
- • Reduced inflammation markers
- • Waist circumference reduction
Expected Dosing Schedule
Based on Phase 2 trials, Retatrutide uses dose escalation to minimize side effects:
Note: Final dosing will be determined by Phase 3 trials and FDA approval. Some patients may achieve goals at lower doses.
Side Effects
Common (GI-Related)
- • Nausea (most common, dose-dependent)
- • Diarrhea
- • Vomiting
- • Constipation
- • Decreased appetite
Trial Observations
- • Side effects similar to other GLP-1s
- • Most resolved with continued use
- • Dose escalation reduces severity
- • Low discontinuation rates
- • No major safety concerns identified
Glucagon effect: Unlike some concerns, the glucagon component did not raise blood sugar in trials. The GLP-1 and GIP components effectively counterbalanced any glucose-raising effects.
Development Timeline
Retatrutide vs Current Options
| Drug | Mechanism | Weight Loss | Company |
|---|---|---|---|
| Retatrutide | GLP-1 + GIP + Glucagon | ~29% | Eli Lilly |
| Zepbound/Mounjaro | GLP-1 + GIP | ~18-21% | Eli Lilly |
| Cagrisema | GLP-1 + Amylin | ~22-25% | Novo Nordisk |
| Wegovy | GLP-1 only | ~15-17% | Novo Nordisk |
Frequently Asked Questions
Is Retatrutide better than Mounjaro?
Recent Phase 3 data suggests Retatrutide is superior, demonstrating 28.7% average weight loss compared to Mounjaro's 21%. The additional glucagon activity likely drives this increased efficacy.
Can I get Retatrutide now?
Retatrutide is not yet approved or available. It's currently in Phase 3 trials. Some research chemical suppliers may sell "research-grade" versions, but these are unregulated, potentially dangerous, and not recommended.
Will Retatrutide be expensive?
Pricing hasn't been announced, but expect it to be similar to or higher than Mounjaro/Zepbound ($1,000-1,500/month without insurance). Eli Lilly will likely price it as a premium next-generation therapy.
What indications is Retatrutide being studied for?
Phase 3 trials are evaluating Retatrutide for obesity/overweight, Type 2 diabetes, and MASH (metabolic dysfunction-associated steatohepatitis, formerly NASH). It may receive multiple FDA approvals for different conditions.
Prepare for the Future of Weight Loss
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