Key Takeaway:
- Retatrutide delivered significant weight loss in the Retatrutide weight loss trial, with the 12 mg dose reducing body weight by 18.8% on average over 80 weeks.
- Blood sugar and cardiometabolic measures improved, including HbA1c, blood pressure, lipid profiles, and inflammation markers.
- The drug remains unapproved, with gastrointestinal side effects such as diarrhea and nausea among the most common adverse events.
Retatrutide, an investigational weight-loss drug from Eli Lilly, helps adults with obesity and type 2 diabetes lose substantial weight while improving blood sugar and other cardiometabolic measures, according to new phase 3 results published in The Lancet.
Trial Shows Substantial Weight Loss At Higher Doses
The 80-week Retatrutide weight loss trial, known as TRIUMPH-2, included 2,047 adults across eight countries, including India, with a body mass index of at least 27 and type 2 diabetes. Of those, 1,152 were randomly assigned to receive weekly retatrutide or placebo alongside dietary and physical activity counseling.
Participants receiving 4 milligrams of retatrutide lost an average of 11.9% of their body weight, compared with 16.8% at 9 milligrams and 18.8% at 12 milligrams. The placebo group lost 5.1%.
At the 12-milligram dose, 47% of participants lost at least 20% of their starting weight, while 31% lost at least 25%. In the placebo group, those figures were 6% and 3%, respectively.
“Retatrutide demonstrated substantial reduction in body weight alongside glycaemic control and cardiometabolic risk factors,” the researchers said, while noting that its safety profile was generally similar to medicines with GLP-1 receptor activity.
Triple-Hormone Drug Also Improves Blood Sugar
Retatrutide activates three hormone receptors: GLP-1, GIP, and glucagon. In the Retatrutide weight loss trial, this differs from semaglutide-based medicines that primarily activate GLP-1 and tirzepatide, which targets GLP-1 and GIP. The glucagon component is intended to increase energy expenditure in addition to affecting appetite and metabolism.
Blood sugar measures also improved during the trial. At the 12-milligram dose, 72% of participants reached an HbA1c of 6.5% or lower, compared with 29% in the placebo group. HbA1c reflects average blood sugar over roughly the previous two to three months.
Researchers also reported improvements in blood pressure and lipid profiles, along with reductions in high-sensitivity C-reactive protein, a marker associated with inflammation.
Eli Lilly, which funded the study and is developing retatrutide, said participants receiving the highest dose lost an average of 49.6 pounds, or 20.8%, over 80 weeks. The company plans to submit a U.S. regulatory application in 2027.
Also Read: 8 Weight Loss Drugs for Those struggling with diet and obesity
Gastrointestinal Side Effects Remain Common
The most frequently reported adverse events were gastrointestinal. Diarrhea affected 27% to 34% of participants receiving retatrutide, compared with 13% receiving placebo, while nausea occurred in 14% to 28% of retatrutide recipients and 8% of those receiving placebo.
Seven deaths occurred during the trial: two among participants receiving 4 milligrams, three receiving 9 milligrams, one receiving 12 milligrams, and one receiving placebo. Investigators judged the deaths unrelated to the study intervention.
Retatrutide remains investigational and has not been approved by any regulatory agency. Lilly says the Retatrutide weight loss trial is legally available only to participants in its clinical trials.
Separate research presented at the European Association for the Study of Diabetes meeting in Milan examined weight-loss drugs and pregnancy outcomes among women with type 2 diabetes. Researchers said the available evidence did not show an association with adverse pregnancy outcomes in most cases but stressed that major evidence gaps remain.
