GLP-1s Could Yield Major Benefits for Achy Knees

“Looking at data from several thousands of patients, we found that those taking a GLP-1 were significantly less likely to end up needing a knee replacement, and the benefit grew the longer they took them,” says senior author Jay Karri, MD, an assistant professor in neurology, anesthesiology, and orthopedic surgery at the University of Maryland School of Medicine in Baltimore.

Given that the “only definitive treatment is major surgery” for knee osteoarthritis, that’s a finding worth taking seriously, says Dr. Karri.

Adults Taking Wegovy or Zepbound for 3 Years Were Less Likely to Get a Knee Replacement

Researchers analyzed electronic health records from a global healthcare database to identify adults diagnosed with knee osteoarthritis between January 1, 2010, and December 31, 2024.

Researchers compared those who had prescription records for GLP-1 drugs with similar people who did not, then tracked how many went on to have knee replacement surgery one, three, five, and eight years after diagnosis.

The researchers used a statistical method called propensity score matching, which allowed them to balance the GLP-1 and non-GLP-1 groups. This accounted for factors including age; sex; race; other bone, joint, or connective-tissue conditions; obesity-related conditions; body mass index; and healthcare access.

“People who took the newer GLP-1s, Wegovy [semaglutide] and Zepbound [tirzepatide], for three years were nearly 5 percentage points less likely to need a knee replacement over eight years compared to similar patients not on these drugs,” says Karri.

That translates to roughly 5 fewer knee replacements per 100 people compared with similar adults not taking these drugs.

People taking either drug for just one year had a 3.4 percentage point lower risk, and taking any type of GLP-1, including older drugs, reduced the risk between 2.8 and 3.25 percent.

“Across a population the size of the United States, the same numbers translate into many thousands of operations avoided each year,” says Derek Amanatullah, MD, PhD, an assistant professor of orthopedic surgery at Stanford Medicine in California.

How GLP-1s Could Lower the Risk of Knee Replacement Surgery

Because the study is observational, it can’t prove that taking the drugs directly lowered the risk of knee replacement surgery. But any potential benefit could be explained by a combination of reasons, says Karri:

• Less weight means less pressure on the knees. Weight loss can reduce the mechanical stress placed on an arthritic knee, which may help ease pain and slow cartilage deterioration over time.
• GLP-1s may help calm inflammation. These medications may reduce inflammatory signals in joint tissue that contribute to arthritis pain and progression.
• They may help protect cartilage. Some evidence suggests GLP-1s could help slow cartilage breakdown, although this study did not include imaging to prove that.
• GLP-1s may reduce pain signals. The medications may affect pain pathways in the joint and nervous system, which could help people function better and delay or avoid surgery.

Dr. Amanatullah agrees that a few factors could be involved, but that it’s likely “weight loss is doing most of the work.”

He points out that “anything that reduces pain, including weight loss, can defer or avoid an operation without changing the underlying arthritis at all. That’s worth keeping in mind before we call this disease modification,” he says.

Study Strengths and Limitations

A major strength of the study is its size. After matching, the groups ranged from more than 13,000 people in the three-year Wegovy or Zepbound group to more than 42,000 people in the one-year any-GLP-1 group. The study also looked at longer-term outcomes and tried to compare people with similar baseline weight and obesity-related diagnoses.

Michael Kheir, MD, a clinical assistant professor and orthopedic surgeon at the University of Michigan Health in Ann Arbor, points out some limitations still need to be considered.

Patients receiving GLP-1 drugs in 2010 may have been taking them for different reasons, at different doses, and for shorter durations than people receiving GLP-1s more recently, says Dr. Kheir, who was not involved in the study.

The database also did not include some details that would help explain the findings, including X-rays, arthritis severity, pain scores, functional status, inflammatory markers, physical activity, frailty, or weight changes over time. Researchers also relied on prescription records, which don’t prove that people took the medication as prescribed.

“We don’t know if patients on GLP-1s had less arthritis to begin with compared to counterparts,” says Kheir. Differences in overall health, comfort with injections, access to care, or surgical eligibility could also have influenced who ultimately had knee replacement, he says.

These findings alone aren’t enough to start recommending newer GLP-1s because they reduce the risk of knee replacement, says Amanatullah.

What People With Knee Arthritis and Extra Weight Can Do Now

“If you have knee osteoarthritis and are living with obesity or a metabolic condition like type 2 diabetes, this research is another reason to take metabolic health seriously, not just for your heart and blood sugar, but for your joints too,” Karri says.

For the right patient, a GLP-1 can be a legitimate tool, says Amanatullah. “What is genuinely new about these drugs is that they make meaningful, sustained weight loss achievable for many people who could not get there before.”

Still, GLP-1s may not be appropriate for everyone with knee pain, and besides, these drugs can cause side effects and be difficult to access, says Karri.

Experts recommend physical activity, too, even though knee arthritis can make that challenging.

“The broader takeaway is this: Weight and metabolic health are not separate from musculoskeletal health. They are central to it,” says Karri. Keeping this in mind and treating accordingly may help people avoid total knee replacement, he says.