23h • General discussion
Retatrutide Phase 3 Results: 28.7% Weight Loss + Inflammation Benefits 🔥
Alright, so Lilly dropped their TRIUMPH-4 Phase 3 data yesterday for retatrutide.
28.7% weight loss. 71 pounds average. At 68 weeks.
If you've been paying attention to triple agonists, this shouldn't be surprising. The Phase 2 data already showed us where this was headed. But now we have the Phase 3 confirmation.
Here's what happened:
445 people with obesity and knee osteoarthritis. Split into three groups - 9mg retatrutide, 12mg retatrutide, and placebo.
The 12mg group lost an average of 71.2 pounds. That's 28.7% of their starting weight.
Compare that to tirzepatide's ~21% in Phase 3. That's 8 percentage points higher. The glucagon agonism makes the difference - you're not just suppressing appetite, you're ramping up energy expenditure and fat oxidation.
Why triple agonists hit different:
Retatrutide is GIP + GLP-1 + Glucagon. You already know GLP-1 from semaglutide. You know the dual combo from tirzepatide. The glucagon piece is what pushes this into a different category.
- GLP-1 = appetite control
- GIP = metabolic optimization
- Glucagon = fat-burning accelerator
You're hitting all three mechanisms simultaneously.
The inflammation piece is wild:
This trial was designed for knee osteoarthritis, not just weight loss. The pain results were massive:
- 76% reduction in pain scores
- 74% improvement in physical function
- 12% of people completely pain-free by week 68
But here's what's interesting - this wasn't just about losing weight and reducing load on the joints. Retatrutide crushed inflammatory markers across the board. hsCRP dropped significantly. Triglycerides down. Blood pressure down 14 mmHg.
Each component has anti-inflammatory effects. GLP-1 reduces pro-inflammatory cytokines. GIP has protective effects on bone and cartilage. Glucagon ramps up fat burning, and less adipose tissue means less inflammatory signaling.
You're not just taking pressure off the knee - you're turning down systemic inflammation that's driving the pain in the first place.
Side effects:
Same as other GLP-1 agonists. Nausea (43%), diarrhea (33%), vomiting (21%).
New addition: dysesthesia/tingling in 21% on 12mg. Lilly says mostly mild.
How it stacks up:
- Semaglutide: ~15% weight loss
- Tirzepatide: ~21% weight loss
- Retatrutide: 28.7% weight loss
The progression is clear. Single → dual → triple agonists. Each step adds mechanisms and efficacy.
28.7% is the new benchmark. Seven more Phase 3 trials complete in 2026. The bar just got raised.
Read The Full Substack Article: https://derekpruski.substack.com/p/retatrutide-phase-3-287-weight-loss
Compare current research options: PeptidePrice.store
Questions drop them below? I think we all knew this but, the inflammation benefits are good to see!
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Retatrutide Phase 3 Results: 28.7% Weight Loss + Inflammation Benefits 🔥
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