This positions the therapy among the most powerful weight-loss medicines currently in development.
The Phase 3 TRIUMPH-1 study evaluated retatrutide, a once-weekly injectable triple hormone receptor agonist, in adults with obesity or overweight and at least one weight-related condition, but without diabetes. The medicine targets GIP, GLP-1 and glucagon receptors simultaneously.
At the highest 12 mg dose, participants lost an average 31.9 kg, or 28.3% of body weight, over 80 weeks. Nearly 45% of participants on the 12 mg dose achieved at least 30% weight reduction, a level typically associated with bariatric surgery outcomes.
Participants with severe obesity who continued treatment in a two-year extension study achieved average weight loss of 38.5 kg, or 30.3%, at 104 weeks.
Even at the lowest 4 mg dose, reached through a single dose-escalation step, participants lost an average 21.4 kg, or 19% of body weight, while showing lower discontinuation rates due to adverse events than placebo.
Ania Jastreboff, Director of the Yale Obesity Research Center (Y-Weight), and lead investigator, said: “Every dose of retatrutide resulted in clinically meaningful weight reduction for nearly all participants, and people with severe obesity on the highest dose lost on average 30% of their body weight over two years.” Lilly said retatrutide also improved several cardiometabolic risk markers, including waist circumference, triglycerides, blood pressure and inflammatory markers.
Jastreboff said treatment with retatrutide not only resulted in robust weight reduction, but also in clear improvements in assessed cardiometabolic health measures.
“For patients I see in clinic, retatrutide may potentially be a highly impactful future tool to treat their obesity and transform their health trajectory.”