Patients with diabetes who receive metformin exhibit 24% lower risk for osteoarthritis
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Key takeaways:
- Metformin may inhibit osteoarthritis development in patients with type 2 diabetes.
- The findings “lay the foundation” for future studies to determine if metformin may be an effective drug for OA, the researchers said.
Patients with type 2 diabetes who undergo metformin therapy demonstrate a 24% lower risk for osteoarthritis, compared with those who received sulfonylurea, according to data published in JAMA Network Open.
“There are nice preclinical studies that demonstrate that treatment with metformin can prevent the onset of osteoarthritis in animals that have had destabilization of the medial meniscus, which leads to OA over time,” Matthew C. Baker, MD, MS, clinical chief and assistant professor of medicine in the division of immunology and rheumatology at Stanford University, told Healio. “Based on these observations, we wanted to see if there was an epidemiological signal for benefit of treatment with metformin in humans.”
To investigate potential associations between metformin and the development of OA, Baker and colleagues conducted a retrospective cohort study analyzing data from the Optum Clinformatics Data Mart Database. Patients’ data were included in the analysis if they were aged 40 years or older and had at least 1 year of enrollment in the database before being diagnosed with diabetes and receiving either metformin or a sulfonylurea. Patients were excluded if they had type 1 diabetes, received therapy before being diagnosed with diabetes or if they began therapy by receiving both metformin and sulfonylurea.
Included patients were split into two groups for analysis. The first group received metformin for at least 90 days, while the control group received a sulfonylurea for at least 90 days. The main endpoint was the time to diagnosis of OA beginning 90 days following the initiation of therapy. The second endpoint of interest was the time to joint replacement beginning 90 days from the beginning of therapy. Additional outcomes included receiving a diagnosis of OA, undergoing joint replacement procedures, ceasing therapy, beginning therapy with a different diabetes drug or no longer being in the database.
Each group contained 20,937 patients. According to the researchers, patients who had received metformin demonstrated a 24% reduced risk of developing OA compared with patients who were treated with a sulfonylurea (adjusted HR = 0.76; 95% CI, 0.68-0.85). There was no significant difference between groups regarding the likelihood of requiring a joint replacement (aHR = 0.8; 95% CI, 0.5-1.27).
The risk for OA remained lower in the metformin group, vs. sulfonylurea, in the sensitivity analysis (aHR = 0.77; 95% CI, 0.65-0.9). The risk for joint replacement additionally remained not statistically significant (aHR = 1.04; 95% CI, 0.6-1.82) in the sensitivity analysis.
“We found that patients treated with metformin had a lower incidence of OA compared with controls,” Baker said. “This is not enough data to suggest using metformin in the clinic yet for OA, but it does lay the foundation for a future, prospective, interventional trial to determine if metformin might be an effective therapeutic for OA.
“Osteoarthritis affects over 50 million people in the U.S., and to date, there are no drugs available that prevent, slow or stop the progression of the disease,” he added. “This paper suggests that metformin has the potential to do this, and we are excited about future work in this space.”
Perspective
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Osteoarthritis is the most common form of arthritis, which affects more than 32.5 million people in the United States. Our current approach to treatment is based on relieving symptoms. No agents have been identified which stop development, or slow or reverse the disease.
Metformin may have beneficial effects on inflammation, aging, cancer, weight reduction and immunomodulation. Several studies have suggested a potential protective mechanism through activation of AMP activated protein kinase signaling, thereby decreasing metalloproteinase, which would reduce chondrocyte apoptosis and potentially help with the chondroprotective and anti-inflammatory properties of mesenchymal stem cells.
Potential limitations of the study include the fact that it was a retrospective analysis, as well as a lack of data on BMI. Studies have shown only modest weight loss with metformin, and patients who had weight loss by diet and exercise did not decrease their risk for developing OA. There were no data on physical activity or history of trauma to affected joints. The study only evaluated patients who were on metformin for diabetes, making it difficult to extrapolate to the general population.
Furthermore, results may have been affected by the study population being on Medicare, which may not be representative of the general population. Additionally, the sulfonylurea group was smaller than the metformin population.
Although these data suggest that metformin may have a protective effect on the development of OA, more data is needed, particularly with a study designed to determine if treatment with metformin would prevent or treat patients with OA.
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Baker MC, et al. JAMA Netw Open. 2023;doi: 10.1001/jamanetworkopen.2023.3646.
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