Eli Lilly’s experimental weight-loss medication retatrutide helped people with Type 2 diabetes lose as much as 60 pounds, or roughly 23% of their body weight, in a late-stage clinical trial published Tuesday in The Lancet.
The results represent the largest weight reduction reported so far in a medication trial involving people with Type 2 diabetes, according to the researchers.
Retatrutide is not yet approved by the U.S. Food and Drug Administration, but the findings could strengthen its position as one of the most closely watched drugs in the next generation of obesity and diabetes treatments.
Significant Weight Loss in Diabetes Trial
The study involved more than 1,110 adults with Type 2 diabetes. Participants had an average starting weight of approximately 234 pounds and an average BMI of about 38.
Patients were randomly assigned to receive one of three weekly doses of retatrutide or a placebo for 80 weeks.
By the end of the study, more than half of the participants had reduced their BMI to below 30, the threshold used to classify obesity.
For comparison, previous clinical trials have reported weight reductions of up to about 10% with semaglutide and 15% with tirzepatide among people with Type 2 diabetes. Researchers caution that these figures cannot be considered direct comparisons because the medications were tested in separate trials.
Dr. Susan Spratt, an endocrinologist at Duke Health who was not involved in the study, described the results as a potentially important development in diabetes treatment.
She noted that some commonly used diabetes medications, including insulin, can contribute to weight gain, making weight management more difficult for certain patients.
Retatrutide Works Differently From Current GLP-1 Drugs
Retatrutide belongs to a newer class of medications known as a triple agonist.
Like semaglutide, it activates the GLP-1 pathway. However, retatrutide also targets GIP and glucagon receptors, giving it three hormonal targets.
Tirzepatide, sold under brands including Mounjaro and Zepbound, acts on two hormonal pathways, GLP-1 and GIP.
Researchers believe the additional glucagon activity may contribute to retatrutide’s ability to produce substantial weight loss.
Strong Results Also Seen in People Without Diabetes
A separate study published in the New England Journal of Medicine found similarly significant weight loss among people who were overweight or had obesity but did not have Type 2 diabetes.
After 80 weeks, participants lost as much as 70 pounds, representing about 25% of their body weight on average.
Among a subgroup of participants with severe obesity, weight loss reached approximately 85 pounds, or 30% of body weight, after 104 weeks.
That result was the largest weight reduction reported in a medication trial and was comparable to the amount of weight loss sometimes associated with bariatric surgery.
Blood Sugar Also Improved
Retatrutide was also effective at improving blood glucose control among participants with Type 2 diabetes.
The medication reduced A1C levels by as much as 1.6 percentage points, compared with a reduction of approximately 0.2 percentage points among people receiving the placebo.
A1C measures average blood sugar levels over roughly the previous two to three months.
As many as 40% of participants receiving retatrutide achieved an A1C below 5.7%, the level below which a person is generally considered not to have diabetes or prediabetes.
Dr. Michelle Ponder of Duke University School of Medicine, who was not involved in the trial, said the findings were encouraging but cautioned that the medication’s potency may not make it appropriate for everyone.
People with relatively mild diabetes or only modest weight concerns may be able to use existing treatments instead, she said.
Side Effects Similar to Other GLP-1 Medications
The trial also found side effects broadly similar to those associated with other medications in the GLP-1 family.
The most frequently reported problems included nausea, diarrhea, constipation and vomiting.
Lilly said most side effects were mild to moderate. Around 8% of participants receiving the highest retatrutide dose discontinued treatment, compared with approximately 5% of those taking the placebo.
Researchers continue to study the drug’s longer-term safety and potential benefits.
Retatrutide Could Have Additional Health Benefits
Beyond weight loss and blood sugar control, earlier research has suggested that retatrutide may help reduce the severity of obstructive sleep apnea and improve pain associated with knee osteoarthritis.
Other research has also raised the possibility of cardiovascular benefits, although further studies are needed to establish the drug’s broader effects.
FDA Approval Has Not Yet Been Granted
Eli Lilly has not yet submitted retatrutide to the FDA for approval. The company has said it expects to seek regulatory approval in the coming year.
Meanwhile, unauthorized versions of retatrutide have reportedly appeared through some online wellness businesses, medical spas and compounding operations.
Lilly has taken legal action against companies accused of selling unapproved versions of the experimental drug.
Until regulatory approval and additional clinical data are available, retatrutide remains an investigational treatment rather than an approved medication for routine patient use.