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

Read the full story: Major Weight Loss and Knee-Pain Relief Seen With New Eli Lilly Drug (NY Times)

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.

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.

Arthritis experts said they were impressed by the effects of retatrutide on knee pain, especially added to the significant weight loss in participants.

Dr. MaCalus Hogan, chair of orthopedic surgery at the University of Pittsburgh Medical Center, said the results are “a huge step forward in weight loss management and relief of orthopedic pain.”

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.

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.

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.

You gotta show the numbers . Up to 28.7% weight loss on the highest dose.

More details in their press release:

In an additional post-hoc analysis, 14.1% of patients on retatrutide 9 mg and 12.0% patients on retatrutide 12 mg were completely free of knee pain at 68 weeks compared to 4.2% on placebo, based on the observed efficacy estimand data.

https://investor.lilly.com/news-releases/news-release-details/lillys-triple-agonist-retatrutide-delivered-weight-loss-average

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I just wish they’d show some additional numbers, e.g.:

  • Percent of body fat loss
  • Percent of muscle loss
  • Percent of visceral fat loss

Interesting:

  • 09 mg retatruide = 14.1% patients free of knee pain
  • 12 mg retatruide = 12.0% patients free of knee pain
  • 00 mg retatruide = 04.2% patients free of knee pain
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More results coming in 2026

Discontinuation rates due to adverse events were 12.2% and 18.2% with retatrutide 9 mg and 12 mg, respectively, compared to 4.0% with placebo. These rates were highly correlated with baseline BMI and included discontinuations for perceived excessive weight loss.

Reading between the lines: the drug at that dose was almost too effective for weight loss. The other hint is that Lilly updated the inclusion criteria for retatrutide to people with BMI>35 only.

If that wasn’t clear before, these weight loss numbers are now squarely in competition with bariatric surgery numbers, with no indication of plateau after 68 weeks.

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Do we have any idea why this reduces knee pain? Is it just weight loss, or is there another mechanism?

Well, on top of the weight loss (which does make a difference in joint pain) it’s got to do with reduction in inflammation also. It’s known that GLP1’s reduce inflammation.

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