Retatrutide posts the largest average weight loss yet in a phase 3 trial
Lilly's triple-hormone peptide, acting on GIP, GLP-1 and glucagon receptors, also eased knee pain in people with obesity and knee osteoarthritis.
What's new
TRIUMPH-4 topline: 28.7% average weight loss at 68 weeks on 12 mg retatrutide in adults with obesity and knee osteoarthritis, plus large drops in knee pain scores.
Why it matters
It pushes average drug-induced weight loss close to what some bariatric surgery studies report.
What's next
Seven more TRIUMPH phase 3 readouts are due, including trials in people without knee disease.
Retatrutide, an experimental once-weekly peptide from Eli Lilly, led to an average weight loss of 28.7% after 68 weeks at its highest dose in TRIUMPH-4, the first of its phase 3 trials to report.
One peptide, three receptors
| Receptor | Effect linked to it |
|---|---|
| GLP-1 | Appetite, insulin release |
| GIP | Insulin release, fat tissue signalling |
| Glucagon | Energy use, liver fat |
Adding glucagon activity is the new part. Glucagon raises blood sugar on its own, but in combination it appears to increase energy expenditure and reduce liver fat.
The trial
TRIUMPH-4 enrolled adults with obesity and knee osteoarthritis. Besides weight, it measured knee pain and physical function, which improved substantially compared with placebo.
Watch points
- Higher discontinuation from side effects at the top dose than at lower doses.
- Some participants lost so much weight that they left the trial for that reason.
- Heart-rate increases seen in earlier studies need long-term follow-up.
Context
Earlier phase 2 data had already pointed to around 24% average weight loss at 48 weeks. TRIUMPH-4 is a specific population; the trials in broader groups will show whether the number holds.
