Retatrutide: The Triple Agonist That Lost 71 lbs in Trials
Retatrutide (LY3437943) is Eli Lilly's triple GIP+GLP-1+glucagon agonist in Phase 3. Phase 3 results show up to 71 lbs average weight loss. Here is what patients need to know.
Retatrutide is the drug that may redefine how the medical world thinks about weight loss. In one Phase 3 clinical trial, participants lost an average of 71.2 lbs (32.3 kg) over 68 weeks. That is the highest average weight loss ever recorded for any drug in any clinical trial.
It is not yet available. But understanding what it is and what the data shows is worth doing now.
What is retatrutide?
Retatrutide (development code LY3437943) is a once-weekly subcutaneous injection developed by Eli Lilly. It is sometimes called the "triple agonist" or "triple G" because it activates all three of the following receptors:
- GIP (glucose-dependent insulinotropic polypeptide) - stimulates insulin, regulates fat metabolism
- GLP-1 (glucagon-like peptide-1) - suppresses appetite, slows gastric emptying, stimulates insulin
- Glucagon receptor - increases energy expenditure, promotes fat breakdown in the liver
Tirzepatide (Mounjaro/Zepbound) activates GIP and GLP-1. Retatrutide adds the glucagon receptor on top of those two. That third mechanism is believed to drive the additional metabolic benefit.
What do the Phase 2 results show?
Phase 2 results, published in The New England Journal of Medicine in June 2023, evaluated retatrutide in 338 adults with obesity over 48 weeks.
Results at 48 weeks:
- 12 mg group: 24.2% mean weight loss
- 8 mg group: 22.8%
- 4 mg group: 17.1%
- Placebo: 2.1%
At 24 weeks, the 12 mg group had already lost 17.5% of body weight. For context, Wegovy's full 68-week trial produces around 15–17% average weight loss.
What do the Phase 3 results show?
Lilly has been running the TRIUMPH Phase 3 program since 2023. Key results announced so far:
TRIUMPH-4 (Obesity + knee osteoarthritis)
- Phase 3 results announced December 11, 2025
- 68 weeks
- 12 mg dose: average weight loss of 71.2 lbs (32.3 kg)
- Also showed 75.8% average reduction in knee pain (WOMAC pain score at 9 mg)
- This is the first weight loss drug to demonstrate both substantial weight reduction and significant joint pain relief
TRIUMPH (Type 2 Diabetes)
- Phase 3 results announced March 19, 2026
- Met primary endpoint: significant A1C reduction and weight loss in T2D patients
The main obesity Phase 3 trial results are still pending. Those will be the pivotal data for an FDA submission.
How does retatrutide compare to Zepbound?
| Drug | Mechanism | Phase | Avg. weight loss |
|---|---|---|---|
| Zepbound 15 mg | GIP + GLP-1 | ✅ Approved | ~48 lbs (21.8%) over 72 weeks |
| Retatrutide 12 mg | GIP + GLP-1 + Glucagon | Phase 3 | ~71 lbs (32.3%) over 68 weeks |
These numbers are from different trials in different patient populations, so they cannot be compared directly. But the scale of the difference is striking.
What are the side effects?
Phase 2 and Phase 3 data show a side effect profile consistent with the broader GLP-1 class:
- Nausea (most common)
- Diarrhea
- Vomiting
- Constipation
Gastrointestinal side effects were dose-dependent - more common at higher doses - but generally mild to moderate and decreased over time. No unexpected safety signals emerged across the trials.
When will retatrutide be available?
As of March 2026, retatrutide remains in Phase 3 trials. The main obesity pivotal trial data needs to be submitted to the FDA before a review can begin. The most optimistic scenario for FDA approval is late 2027.
It is not currently available outside of clinical trials. Any product claiming to be retatrutide is not legitimate.
Bone and joint benefits
The TRIUMPH-4 data is notable beyond weight loss. For patients with obesity and knee osteoarthritis, the 75.8% average reduction in joint pain alongside the weight loss represents a genuinely new combination of benefits. This may lead to a specific indication for obesity with musculoskeletal complications.
Final takeaway
Retatrutide is a once-weekly triple agonist in Phase 3 that has produced the highest average weight loss of any drug ever studied in a clinical trial. It is not yet FDA approved. Approval is not expected before 2027. When it does reach patients, it will likely represent the most powerful pharmacological weight loss option available.
Consult your healthcare provider before making any decisions about treatment changes based on pipeline data.
Sources
- Retatrutide FDA history: drugs.com/history/retatrutide.html
- Phase 2 results: Jastreboff AM, et al. Triple–Hormone-Receptor Agonist Retatrutide for Obesity. N Engl J Med. 2023;389:514–526
- TRIUMPH-4 Phase 3 results: Eli Lilly press release, December 11, 2025
- TRIUMPH T2D Phase 3: Eli Lilly press release, March 19, 2026
FAQ
What is retatrutide?
Retatrutide is an investigational once-weekly injection developed by Eli Lilly that activates three hormone receptors simultaneously: GIP, GLP-1, and glucagon. It is currently in Phase 3 clinical trials and is not yet FDA approved.
How much weight does retatrutide cause you to lose?
Phase 2 trials showed up to 24.2% average weight loss at 48 weeks. A Phase 3 trial (TRIUMPH-4) showed an average of 71.2 lbs (32.3 kg) lost over 68 weeks at the 12 mg dose in adults with obesity and knee osteoarthritis.
When will retatrutide be available?
Retatrutide is still in Phase 3 trials as of early 2026. FDA approval is not expected before 2027 at the earliest.
Is retatrutide better than Mounjaro or Zepbound?
Based on clinical trial data so far, retatrutide appears to produce more weight loss than tirzepatide (Mounjaro/Zepbound). Zepbound produced an average of about 48 lbs in its pivotal trial. Retatrutide produced 71 lbs in one Phase 3 trial. However, the trials are not directly comparable and final Phase 3 obesity results are still pending.