A widely prescribed diabetes medication has demonstrated significant efficacy in reducing knee osteoarthritis pain, potentially offering a new treatment option for millions suffering from this debilitating condition.
A collaborative study between Monash University's School of Public Health and Preventive Medicine, the Menzies Institute for Medical Research at the University of Tasmania, and the Department of Rheumatology at Alfred Hospital found that metformin substantially reduced pain and improved function in overweight individuals with knee osteoarthritis.
The six-month randomized controlled trial, recently published in JAMA, involved 107 overweight, non-diabetic participants over 40 years old who had experienced knee pain for at least six months. Participants in the treatment group received up to 2,000 mg of extended-release metformin daily, while the control group received an identical-looking placebo.
"Metformin works in a number of ways on the knee, including affecting low-grade inflammation and other metabolic pathways that are important in knee osteoarthritis," explained Professor Flavia Cicuttini, the study's corresponding author and Head of Rheumatology at Alfred Hospital. "It is a different way to treat knee osteoarthritis pain."
Significant Pain Reduction and Functional Improvement
Using a 100-mm visual analog scale (VAS) to measure pain intensity, researchers found that participants taking metformin experienced a 31.3-point reduction in knee pain after six months, compared to an 18.9-point reduction in the placebo group. This represents a moderate effect size of 0.43, indicating a clinically meaningful difference between the groups.
Beyond pain relief, the metformin group also reported significantly improved joint stiffness and function compared to those taking placebo. These improvements could have substantial implications for patients' quality of life and ability to maintain physical activity.
A Potential Alternative to Surgery
Knee osteoarthritis affects hundreds of millions of people worldwide, with more than half of sufferers being overweight or obese. Current treatment options are limited, with many patients ultimately requiring knee replacement surgery when pain becomes unbearable.
"At first glance this may seem reasonable, but it is a major problem because patient dissatisfaction with knee replacements is already high at between 20 to 30%, even when the operation is technically perfect," Cicuttini noted. "Dissatisfaction rates are highest when the operation is done for early knee osteoarthritis."
The findings suggest that metformin could potentially delay the need for invasive knee replacement surgery by providing effective pain management and improving mobility.
Safety Profile and Accessibility
Metformin has been used as a first-line treatment for type 2 diabetes since the 1950s, with a well-established safety profile. In the study, adverse events were reported in 30% of the metformin group compared to 19% in the placebo group, with the most common side effects being mild-to-moderate diarrhea and abdominal discomfort. No serious adverse events were reported.
"GPs are very familiar with metformin, which is a low-cost, safe medication," said Cicuttini. "It could be provided to patients in addition to other treatments they use and has the potential to delay people having knee replacements before they are absolutely needed."
The researchers also highlighted the potential for metformin to be prescribed via telehealth, making it accessible to patients in regional and remote areas.
Current Treatment Landscape
Existing treatments for knee osteoarthritis focus primarily on symptom management rather than disease modification. Options include pain-relieving medications such as non-steroidal anti-inflammatory drugs (NSAIDs), exercise, weight management, physical therapy, and steroid injections.
Many patients find it challenging to adhere to exercise and weight loss recommendations, while pharmaceutical options often provide only modest benefits. This treatment gap has led many to pursue surgical interventions earlier than might be optimal.
Future Research Directions
While the results are promising, the researchers acknowledge that larger clinical trials are needed to confirm these findings. "Because of the modest sample size, confirmation in a larger clinical trial is warranted," Cicuttini stated.
If confirmed in larger studies, metformin could represent an important addition to the treatment pathway for knee osteoarthritis, particularly for overweight and obese patients who face higher risks of disease progression due to increased joint stress and inflammation.
The repurposing of this well-established diabetes medication for osteoarthritis treatment could provide a cost-effective intervention that improves patient outcomes while potentially reducing healthcare costs associated with premature knee replacement surgeries.
