Most people know the feeling of stiff, aching knees when getting up from a chair.
For many, that soreness comes bundled with carrying extra weight the joints never quite forgive. Losing those pounds is hard, and losing enough to notice in the knees is harder still.
A once weekly injection called retatrutide did both at once.
In two Phase 3 trials published in the New England Journal of Medicine on November 8, about two thirds of patients with obesity and knee osteoarthritis had their knee pain cut in half or more.
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Only 38 percent of patients on placebo reached the same threshold. The trials, called TRIUMPH-4 and TRIUMPH-1-OA, enrolled more than 1,000 adults with obesity and painful knee osteoarthritis.
Retatrutide is made by Eli Lilly and is not yet approved. Phase 3 is the last trial stage before a company can ask the Food and Drug Administration to clear a drug.
What the trials actually measured
Participants received an injection under the skin once a week for about 68 to 80 weeks. At the highest dose, they lost about 24 to 25 percent of their starting body weight.
The placebo group lost only around 4 percent. Pain scores on the standard knee osteoarthritis measure fell about twice as much on retatrutide as on dummy injections.
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One of the trial's lead investigators, Thomas Schnitzer at Northwestern University Feinberg School of Medicine, worked on the knee pain findings. Carrying less weight simply puts less load on the joint, which means less pain and better function.
How retatrutide differs from current weight loss drugs
Retatrutide is a triple hormone receptor agonist. That means it activates three natural hormone targets at once, called GIP, GLP-1 and glucagon, instead of only one or two.
Standard weight loss injections like semaglutide, the active ingredient in Novo Nordisk's Ozempic and Wegovy, typically produce 10 to 20 percent weight loss.
The three-way action in retatrutide may explain the larger drop in body weight seen in these trials.
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The side effects
The downsides look similar to other GLP-1 drugs. Nausea, diarrhea, constipation and vomiting were the most common complaints.
Serious adverse events were more common with retatrutide than with placebo.
Doctors have also flagged muscle loss as a concern with this class of drugs. That matters for people with painful knees, since weak thigh muscles make knee osteoarthritis worse.
Retatrutide is still under FDA review and is not available for weight loss or knee pain outside of clinical trials.
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Anyone with obesity and joint pain can ask their doctor about currently approved weight loss options and standard osteoarthritis care.
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This article is made and published by Ida-Marie Palm Varbæk, who may have used AI in the preparation.