The Eli Lilly logo appears at the company's office in San Diego, California, USA, on November 21, 2025.
Mike Blake | Reuters
Eli Lilly on Thursday said its next-generation anti-obesity drug produced what appears to be the biggest weight loss yet in a late-stage trial while reducing pain from knee arthritis, approving the first of several upcoming studies on the weekly shot.
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 at 68 weeks, looking at all participants, including those who stopped treatment. When evaluating only patients who continued taking the drug, the highest dose produced a 28.7% weight loss on average.
The company said some patients lost so much weight that they decided to drop out of the trial.
“It's amazing,” said Dr. Caroline Apovian, co-director of the Center for Weight Management and Wellness at Brigham and Women's Hospital. “We now have a drug that rivals the benefits of weight loss surgery.”
Apovian said Eli Lilly appears to be positioning the drug strategically for people with severe obesity, or a body mass index greater than 35 or 40. He noted that the company said 84% of patients in the trial had a BMI greater than that number in the trial.
Eli Lilly shares rose more than 3% on Thursday.
This is the first late-stage data on retatrutide, which works differently than existing injections and appears to be more effective. Eli Lilly is betting big on retatrutide as the next pillar of its obesity portfolio after its Zepbound weight-loss shot and upcoming pill. But it is still unclear when the drug might enter the market.
It is a critical part of the drugmaker's plan to maintain its majority market share during Nordisk in the booming market for weight loss and diabetes medications. Some analysts estimate the segment could be worth about $100 billion by the 2030s.
Retatrutide also met the trial's other main goal of reducing pain from knee osteoarthritis (a common condition that wears down joint cartilage, causing pain and stiffness) by up to 62.6% on average across all patients, according to a widely used survey. More than 1 in 8 patients taking the drug were completely free of knee pain at the end of the trial, Eli Lilly said.
One concern with current weight loss medications is that they can cause loss of lean muscle mass. But Apovian said the results show that in severely obese adults, physical function can be improved with retatrutide.
The results appear to exceed Wall Street's expectations. In a note ahead of the findings, BMO Capital Markets analyst Evan Seigerman said his baseline assumption was that the drug would show weight loss of about 20% to 23%, with 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,” Kenneth Custer, president of Lilly Cardiometabolic Health, said in a statement.
In a note Thursday, JPMorgan analyst Chris Schott said retatrutide's tolerability data, or how well patients handle the treatment, is “somewhat worse than Zepbound, although not surprising, in our view.”
About 18 percent of patients receiving the highest dose of the drug discontinued treatment because of side effects, compared with 4 percent of those in the placebo group. Eli Lilly said those dropout rates were “highly correlated” with patients' baseline body mass index and included discontinuations due to “perceived excessive weight loss.”
Among those with a BMI of 35 or higher who took the highest dose, 12% discontinued treatment. Schott said that figure is closer to the dropout rates seen in trials with Eli Lilly's weight-loss drug Zepbound and NordiskThe injection for obesity Wegovy.
In a separate note Thursday, BMO's Seigerman said the discontinuation rates “appear to highlight that the speed and strength of weight loss was excessive for some patients with lower BMI.” But he said “all the results are impressive.”
About 43% of patients receiving the highest dose experienced nausea, while approximately 33% and 20.9% had diarrhea and vomiting, respectively. More than 1 in 5 patients who received the highest dose also experienced dysesthesia, which is an unpleasant nervous sensation. The company said it was generally mild for patients and rarely led them to stop treatment.
The study, called TRIUMPH-4, did not focus solely on weight loss, meaning other trials designed specifically for that outcome could produce different or better results. Eli Lilly expects to report results from seven additional phase three trials of the drug by the end of 2026.
Dubbed the “triple G” drug, retatrutide works by mimicking three hormones that regulate hunger (GLP-1, GIP and glucagon) instead of just one or two like existing treatments. It appears to have more powerful effects 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, uniquely mimics GLP-1.
Higher doses of tirzepatide helped obese patients lose about 20.9% of their body weight on average in late-stage studies, looking at all patients regardless of discontinuations.
As Eli Lilly establishes an advantage in space, its main rival, Novo Nordisk, races 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 similarly uses a three-pronged approach to promote weight loss and regulate blood sugar. But Novo Nordisk's treatment is in a much earlier phase of development, meaning it will be several years before it reaches patients.
