- GLP-1 receptor agonists such as Ozempic, Zepbound, or Mounjaro are used to treat type 2 diabetes and obesity, however, they may also have positive effects on other health conditions.
- Researchers have been examining other potential uses for GLP-1 drugs outside of managing diabetes and weight loss, including treating rheumatic diseases.
- A new study has discovered small amounts of the body’s natural GLP-1 hormone in the body’s synovial fluid, or joint fluid.
- Scientists believe this finding may potentially open up a new treatment option for various forms of arthritis, such as osteoarthritis and rheumatoid arthritis.
Now, a new study published in the journal
For this study, researchers analyzed blood and joint fluid samples from participants of the Inflammation in Arthritis (INART) biobank at Aarhus University Hospital in Denmark. Study participants either had rheumatoid arthritis or spondyloarthritis.
“Arthritis comprises a range of diseases that cause joint pain, inflammation, and reduced quality of life,” Tue Wenzel Kragstrup, MD, PhD, associate professor in the department of biomedicine at Aarhus University, medical specialist in the Department of Molecular Medicine (MOMA) at Aarhus University Hospital in Denmark, and lead author of this study, told Medical News Today.
“While effective treatments exist for some forms [of arthritis], many patients still experience insufficient disease control or side effects. There is therefore a continued need to explore new biological pathways that could lead to improved or complementary treatment strategies,” Kragstrup continued.
Kragstrup said he and his team became interested in GLP-1-based therapies because experimental studies suggest that they may have direct anti-inflammatory and tissue-protective effects in joint disease.
“At the same time, recent clinical studies have reported beneficial effects in conditions such as osteoarthritis and psoriatic arthritis,” he said. “However, from clinical studies alone, it is difficult to know how much of the benefit is due to direct effects in the joint and how much may be explained by weight loss or broader metabolic changes.”
“That is why we wanted to address a basic mechanistic question first: whether GLP-1 is actually present in the joint environment. If GLP-1 is detectable in synovial fluid, that supports the biological plausibility that GLP-1-based therapies could potentially act directly in the joint as well as systemically.”
— Tue Wenzel Kragstrup, MD, PhD
After comparing participants’ blood and joint fluid samples to those from healthy volunteers, researchers detected small amounts of the body’s natural GLP-1 hormone in joint fluid.
“The key finding is that GLP-1 can be detected in synovial fluid,” Kragstrup said. “This suggests that the joint is exposed to circulating GLP-1, but only to a limited extent under physiological conditions. This provides a biological basis for considering whether pharmacological GLP-1 therapies, which achieve much higher systemic levels, could also reach the joint and potentially have local effects.”
Additionally, scientists found that the level of GLP-1 hormone in the synovial fluid is directly tied to the levels in the blood of arthritis patients.
“We observed a clear correlation between GLP-1 levels in blood and in synovial fluid. This suggests that joint levels largely reflect systemic levels, likely through passive distribution from the circulation. This is important because it indicates that any increase in systemic GLP-1 levels (for example through medication) could potentially influence the amount that reaches the joint.”
— Tue Wenzel Kragstrup, MD, PhD
“The next step (in this research) is to find out whether GLP-1-based drugs reach the joints in high enough concentrations to have biological effects there,” Kragstrup continued.
“In collaboration with Steno Diabetes Center, we also plan to analyze blood samples from patients who have either received GLP-1-based treatment or undergone bariatric surgery, to see whether one of these approaches has a stronger effect on inflammation more broadly. This may help us separate effects related to the drug itself from effects related to weight loss and improved metabolism,” he added.
MNT spoke with Jeffrey Zarin, MD, an orthopedic surgeon specializing in joint replacement surgery at Cedars-Sinai Orthopaedics in Los Angeles, CA, about this study, who commented that his first reaction was to be cautious about “over-interpreting” its findings.
“There are many studies that appear in the literature that identify new ideas or pathways for common problems such as arthritis, but often they represent very early stages of research to establish an understanding of the condition,” Zarin explained.
“‘Over-interpretation’ means that people may take this early information and interpret the findings in a way that suggests a treatment plan or improved technology that is not correctly derived from the study findings or outcome,” he told MNT.
“For example, in this study it establishes that GLP-1 and its derivatives have been able to be measured in synovial fluid,” he continued.
“It would be incorrect to conclude that because these proteins are present in joint fluid, that using a medication that affects their levels or efficacy will change the nature of arthritis. In fact, this study shows that the levels of these molecules are significantly lower in joint fluid than in the blood/plasma and may be incidental to the function of the joints.”
— Jeffrey Zarin, MD
“Also, there did not seem to be a difference between patients that had arthritis and those that did not, so conclusions about the effect of GLP-1 on arthritis should also be interpreted cautiously,” Zarin added.
Zarin said it would be appropriate to follow the authors’ suggestion that the next step in their research should be to perform studies to assess whether GLP-1 levels in the joint fluid are correlated with the arthritic condition.
“If there is a correlation, then further studies that assess interventions which can affect the GLP-1 levels and their effects on the symptoms and conditions of arthritis could lead to novel interventions for patients with arthritis utilizing the findings of the studies,” he said.
