Eli Lilly’s investigational retatrutide, a once-weekly triple GIP/GLP-1/glucagon receptor agonist, produced substantial weight loss in the phase 3 TRIUMPH-1 trial, published September 29 in The New England Journal of Medicine. The randomized trial included 2,339 adults with obesity without diabetes, treated for 80 weeks.
Mean weight loss was 17.6% with 4 mg, 23.7% with 9 mg and 25.0% with 12 mg, compared with 3.9% with placebo. At the highest dose, more than one-fifth of participants achieved at least 35% weight loss using the treatment-regimen estimand. The trial also included dedicated subgroups with knee osteoarthritis and obstructive sleep apnea, with significant improvements in pain and apnea-hypopnea events.
The GI safety profile remains important. Gastrointestinal adverse events—including nausea, diarrhea and constipation—were the most common, generally mild or moderate and occurring most frequently during dose escalation. GI events also contributed to permanent dose reductions. Treatment discontinuation due to adverse events increased from 4.1% at 4 mg to 11.1% at 12 mg.
The trial was funded and monitored by Eli Lilly, the manufacturer, and had no active comparator, which the authors identify as a limitation.