Major Weight Loss and Knee-Pain Relief Seen With New Eli Lilly Drug
The maker of Zepbound reported results from a study of retatrutide, which targets three hormones in the body and led to much more weight loss than any approved drug.
www.nytimes.com
By Gina Kolata
Gina Kolata has been reporting on obesity and attempts to treat it for 30 years.
Dec. 11, 2025 Updated 10:24 a.m. ET
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.
Major Weight Loss and Knee-Pain Relief Seen With New Eli
Lilly Drug
Major Weight Loss and Knee-Pain Relief Seen With New Eli Lilly Drug
The maker of Zepbound reported results from a study of retatrutide, which targets three hormones in the body and led to much more weight loss than any approved drug.
www.nytimes.com
12/11/25, 7:52 AM New Eli Lilly Drug Retatrutide Brought Major Weight Loss in Trial - The New York Times
https://www.nytimes.com/2025/12/11/health/eli-lilly-retatrutide-weight-loss-drug.html 1/2
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.
The company will not set a price for retatrutide until it receives Food and Drug Administration approval to
market the drug. An Eli Lilly spokeswoman said it will file for approval following the completion of seven
additional studies of the drug in people with obesity and diabetes. It expects them to be completed next year .
A correction was made on Dec. 11, 2025: An earlier version of this article misstated which Eli Lilly clinical trials will
include a maintenance dose of a weight loss drug. It will be included in trials that are ongoing, not in a completed
trial with patients who also had knee arthritis.
When we learn of a mistake, we acknowledge it with a correction. If you spot an error, please let us know at
[email protected]. Learn more
Gina Kolata reports on diseases and treatments, how treatments are discovered and tested, and how they affect people.
