Eli Lilly’s weight loss drug Retatrutide passes first late-stage trial

Eli Lilly’s logo appears at the company’s office in San Diego, California, USA on November 21, 2025.

Mike Blake | Reuters

Eli Lilly announced Thursday that its next-generation obesity drug appeared to produce the highest levels of weight loss to date while reducing knee arthritis pain in a late-stage trial. This completed the first of several upcoming weekly injection studies.

The highest dose of the drug helped patients with obesity and a type of knee arthritis lose an average of 23.7% of their body weight after 68 weeks when analyzing all participants, including those who discontinued treatment. When evaluating only patients who continued taking the drug, the highest dose resulted in an average weight loss of 28.7%.

the company said Some patients lost so much weight that they decided to stop the study.

“It’s unbelievable,” said Dr. Caroline Apovian, co-director of the Center for Weight Management and Wellness at Brigham and Women’s Hospital. “Now we have a drug that can rival the weight loss benefits of surgery.”

Apovian said Eli Lilly appears to be strategically positioning the drug for people with severe obesity or a body mass index over 35 or 40. She noted that the company said 84% of patients in the study had a BMI above this value.

Shares of Eli Lilly rose more than 3% on Thursday.

It’s the first late-stage data on retatruide, which works differently than existing injections and appears to be more effective. Eli Lilly is betting heavily on retatrutide as the next pillar of its obesity portfolio after the Zepbound weight loss injection and the upcoming pill. However, it is still unclear when the drug might come onto the market.

This is a crucial part of the drugmaker’s plan to maintain its market share majority Novo Nordisk in the booming market for weight loss and diabetes medications. Some analysts estimate the segment could be worth around $100 billion by the 2030s.

Retatrutide also achieved the study’s other primary goal of reducing pain in knee osteoarthritis – a common condition that wears down joint cartilage, leading to pain and stiffness – by up to 62.6% on average when analyzing all patients, based on a widely used survey. More than one in eight patients who took the drug were completely free of knee pain at the end of the study, Eli Lilly said.

One problem with current weight loss medications is that they can cause loss of muscle mass. But Apovian said the results show that retatruide can improve physical function in adults with severe obesity.

The results appear to exceed Wall Street’s expectations. In a note ahead of the results, Evan Seigerman, an analyst at BMO Capital Markets, said that in the base case, he expected the drug to produce about 20% to 23% weight loss and at least a 50% reduction in knee pain.

The company believes retatrutide “could become an important option for patients with significant weight loss needs and certain complications, including knee osteoarthritis,” said Kenneth Custer, president of Lilly Cardiometabolic Health, in a statement.

In a note Thursday, JPMorgan analyst Chris Schott said that retatruide’s tolerability data, or how well patients cope with the treatment, is “slightly worse compared to Zepbound, although not surprising in our view.”

About 18% of patients who received the highest dose of the drug discontinued treatment due to side effects, compared with 4% of those in the placebo group. Eli Lilly said these dropout rates were “highly correlated with patients’ initial body mass index” and included dropouts due to “perceived excessive weight loss.”

Of those with a BMI of 35 or higher who took the highest dose, 12% discontinued treatment. Schott said that number is closer to the dropout rates seen in studies of Eli Lilly’s weight-loss drug Zepbound Novo Nordisk‘s obesity injection Wegovy.

In a separate note Thursday, BMO’s Seigerman said the discontinuation rates “appear to indicate that the rate and magnitude of weight loss was too high in some patients with lower BMIs.” But he said: “All the results are impressive.”

About 43% of patients receiving the highest dose experienced nausea, while about 33% and 20.9% experienced diarrhea and vomiting, respectively. More than one in five patients also experienced dysesthesia, an unpleasant nerve sensation, at the highest dose. The company said it was generally mild for patients and rarely caused them to stop treatment.

The study, called TRIUMPH-4, did not focus solely on weight loss, meaning that other studies specifically designed to address this endpoint could produce different or better results. Eli Lilly expects to report results from seven additional phase 3 studies of the drug by the end of 2026.

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Retatrutide is called a “triple-G” drug and mimics three hunger-regulating hormones – GLP-1, GIP and glucagon – rather than just one or two like existing treatments. This appears to have a stronger effect on a person’s appetite and satisfaction with food than other treatments.

Tirzepatide, the active ingredient in Zepbound, mimics GLP-1 and GIP. Novo Nordisk’s semaglutide, the active ingredient in Wegovy, only mimics GLP-1.

Higher doses of tirzepatide resulted in patients with obesity losing an average of about 20.9% of their body weight in later studies that analyzed all patients regardless of treatment discontinuation.

While Eli Lilly is gaining a lead in this area, its main competitor Novo Nordisk is trying to catch up. In March, Novo Nordisk said it had agreed to pay up to $2 billion for the rights to an early experimental drug from Chinese pharmaceutical company United Laboratories International.

Novo Nordisk’s newly acquired drug is a clear potential competitor to retatrutide because it also takes a three-pronged approach to promoting weight loss and regulating blood sugar. However, Novo Nordisk’s treatment is much earlier in development, meaning it will take several years to reach patients.