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Major Weight Loss and Knee-Pain Relief Seen With New Eli Lilly Drug

December 11, 2025
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Major Weight Loss and Knee-Pain Relief Seen With New Eli Lilly Drug

People with obesity and arthritis taking an experimental obesity drug made by Eli Lilly lost more weight than with any drug now on the market, and they reported relief from their arthritis symptoms, the company announced on Thursday.

The drug, retatrutide, is a next-generation obesity and diabetes medication from Eli Lilly, which already sells Mounjaro for diabetes and Zepbound for weight loss. These drugs catapulted Lilly in November into becoming the first medical company to hit a trillion-dollar valuation.

The clinical trial that found the result lasted 68 weeks and included 445 people with both obesity and knee arthritis. They were randomly assigned to inject one of two doses of retatrutide — nine milligrams or 12 milligrams, once a week, or a placebo.

Participants taking the 12-milligram dose of retatrutide lost an average of 28.7 percent of their body weight, or 71.2 pounds. That is more than the average achieved with Zepbound, which results in a 21 percent average weight loss. It was also more weight loss than is typical with Novo Nordisk’s Wegovy, which averages 15 percent.

Eli Lilly added that 23.7 percent of participants taking the 12-milligram dose lost at least 35 percent of their initial weight.

Participants reported their knee pain on a standard scale, the WOMAC, that goes from 0 to 10, with 10 being worst. Those taking the highest dose of retatrutide reported a pain reduction of 4.4 points, a 74.3 percent reduction in pain, while those taking the placebo reported a reduction of 2.4 points, a 40.3 percent reduction.

WOMAC physical function scores, which measure pain, stiffness and difficulty moving, fell by 4.2 points, a 73.7 percent reduction, in those taking 12 milligrams of retatrutide. Those taking the placebo reported a reduction of 2.1 points, a 35.6 percent reduction.

An Eli Lilly spokeswoman said the study was not designed to answer the question of whether the relief from the pain and from the symptoms of arthritis were more than would have been expected with the weight loss alone.

The most common side effects were like those seen with Zepbound and Wegovy — nausea, diarrhea, constipation and vomiting, which wane over time.

Another side effect was dysesthesia, a painful sensation when the skin is touched. Twenty percent of those taking the highest dose and 8.8 percent of those with the lower dose experienced it. But Eli Lilly said the events were “mostly mild and rarely led to discontinuation” of the treatment.

In all, among those taking the highest dose, 12.1 percent stopped taking the drug because of adverse events — including “perceived excessive weight loss,” the company said. For those taking the placebo, 4.8 percent dropped out of the study because of adverse events.

Retatrutide is sort of a souped-up GLP-1, a class of drugs that has revolutionized the treatment of diabetes, obesity and other conditions.

The Lilly drug affects levels of three hormones involved with regulating appetite, energy balance and metabolism. They are GLP-1, which is the hormone affected by Wegovy and Zepbound; GIP, affected by Lilly’s Zepbound; and glucagon, a hormone that neither Wegovy nor Zepbound targets. Glucagon is released by the pancreas and raises blood sugar levels. It is not clear to researchers why targeting these three hormones had a greater effect than the earlier medications that affect just one or two.

Eli Lilly’s announcement of the arthritis study was a summary of its results, which is required of companies when they have new data that can affect their stock price.

The company said full results would be reported at a medical meeting and published at a later date in a peer-reviewed journal. It added that the full publication also would include results from the current trial when patients took a maintenance dose that was one-third of the highest dose of the drug.

Gina Kolata reports on diseases and treatments, how treatments are discovered and tested, and how they affect people.

The post Major Weight Loss and Knee-Pain Relief Seen With New Eli Lilly Drug appeared first on New York Times.

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