Metformin, Remarkably Versatile, Shown to Reduce Knee Pain

An enduring and versatile mainstay of therapy for type 2 diabetes, metformin never ceases to earn our respect. On Thursday in JAMA, researchers showed this humble drug delivers improvements in knee pain for persons with overweight or obesity and osteoarthritis.

In this six-month study of 107 persons randomized to either placebo or up to 2,000 mg of metformin daily, persons receiving metformin enjoyed a moderate and statistically significant reduction in knee pain. While all of these patients had a BMI greater than 25, none of them had diabetes requiring metformin or any other drug to lower their glucose. The authors of the study drew a careful conclusion:

“These results support use of metformin for treatment of symptomatic knee osteoarthritis in people with overweight or obesity. Because of the modest sample size, confirmation in a larger clinical trial is warranted.”

Consistent with Other Findings

These results are persuasive because of the randomized and placebo-controlled nature of the study. But it is not the only data to suggest metformin might be helpful for knee pain in osteoarthritis.

In particular, we note a 2023 study that showed persons treated with metformin for mild type 2 diabetes had a 25% lower risk of developing osteoarthritis than patients receiving a different type of drug, a sulfonylurea, for the same indication.

In a 2022 review, Yanhong Song, Ziyi Wu, and Ping Zhao wrote that:

“Metformin may be beneficial in the treatment of osteoarthritis by inhibiting inflammation, modulating autophagy, antagonizing oxidative stress, and reducing pain levels.”

In short, the many subtle effects of metformin on metabolic and immunologic health may be adding up to a modest benefit for reducing the symptoms of osteoarthritis. Among its effects is a modest reduction in weight, which is certainly helpful for reducing knee pain from osteoarthritis.

After almost 70 years of use, metformin is a modest little wonder drug that has many ways to impress us.

Click here for the new study and here for further perspective on it. For thoughts about the versatility of metformin, click here.

Knee MRI, photograph by Nevit Dilmen, licensed under CC BY-SA 3.0

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April 26, 2025