Key Takeaway:
- Significant weight loss: Experimental drug retatrutide helped adults with obesity and Type 2 diabetes lose up to 18.8% of their body weight over 80 weeks.
- Improved metabolic health: The treatment reduced blood sugar levels and improved several cardiovascular risk markers.
- Side effects and approval remain concerns: Digestive problems were common, and retatrutide remains investigational pending regulatory review.
Eli Lilly’s experimental weight-loss drug retatrutide helped adults with obesity and Type 2 diabetes lose substantial weight and improve blood sugar control, according to Phase 3 trial results published in The Lancet.
The 80-week TRIUMPH-2 trial involved 1,152 adults who received weekly injections of retatrutide or a placebo. Researchers evaluated whether the drug’s ability to activate three hormone receptors could improve weight management and metabolic health in people facing both conditions.
Triple-Action Drug Delivers Significant Weight Loss
Participants received weekly doses of 4 milligrams, 9 milligrams, or 12 milligrams of retatrutide, or a placebo. The experimental medicine targets receptors for GLP-1, GIP, and glucagon, hormones involved in appetite, insulin response, and energy metabolism.
After 80 weeks, participants receiving the highest dose lost an average of 18.8% of their body weight, compared with 5.1% among those receiving a placebo, according to the study results reported by Medical Xpress. Average weight loss increased with the dose, reaching 11.9% in the 4-milligram group and 16.8% in the 9-milligram group.
Participants with a body mass index of 35 or higher experienced even greater reductions, averaging 21.9% with the highest dose. The findings suggest that retatrutide could offer another treatment option for people whose obesity and diabetes make weight management particularly challenging.
Juan P. Frías, the trial’s principal investigator and medical director of the Los Angeles Institute for Metabolic Research, said in an Eli Lilly statement that the drug reduced both weight and blood sugar substantially.
“Results such as these may change what we set out to achieve with a single therapy for adults living with type 2 diabetes and obesity,” Frías said.
Blood Sugar and Heart Risk Markers Also Improve
Beyond weight reduction, retatrutide improved participants’ long-term blood sugar measurements, known as HbA1c. The treatment lowered HbA1c by approximately 1.4 to 1.5 percentage points, compared with a 0.45-percentage-point reduction reported in the placebo group.
Researchers also observed improvements in several cardiovascular risk markers, including waist circumference, systolic blood pressure and triglyceride levels. These changes may be relevant because obesity and Type 2 diabetes increase the risk of cardiovascular disease.
Kenneth Custer, president of Lilly Cardiometabolic Health, said the findings demonstrate the potential of the treatment.
“TRIUMPH-2 shows what the next generation of cardiometabolic medicine could deliver: substantial weight loss, A1C reduction and improvements across other critical cardiovascular risk factors,” Custer said in the company’s statement.
However, improvements in these measurements do not establish that the drug prevents heart attacks, strokes, or other long-term complications. Researchers will need additional evidence to determine whether the observed benefits translate into better long-term health outcomes.
Digestive Side Effects Remain a Concern
Digestive problems were the most common adverse events reported during the trial. At the highest dose, approximately 34% of participants experienced diarrhea, 28% reported nausea, and 16% experienced vomiting.
Some participants stopped treatment because of adverse events. Discontinuation rates were higher in the 9-milligram and 12-milligram groups than in the placebo group, highlighting the importance of evaluating tolerability alongside weight-loss benefits.
Retatrutide remains an investigational medicine and is not legally available for routine human use, according to Eli Lilly. The company has said it plans to submit an application to the U.S. Food and Drug Administration in the first quarter of 2027.
The trial adds to research into treatments that address obesity and diabetes together. Further regulatory review and research will determine whether retatrutide becomes an approved treatment and how its benefits and risks compare with existing medicines.
