Diabetes drug metformin reduces knee pain in people with overweight or obesity clinical trial shows

A widely prescribed diabetes medication may offer relief for people living with knee osteoarthritis (OA) and overweight or obesity, potentially delaying the need for knee replacement surgery, according to new research led by Monash University.

The clinical trial, published in the Journal of the American Medical Association (JAMA), found that metformin, a drug commonly used in the treatment of type 2 diabetes, significantly reduced knee arthritis pain over a six-month period.

The randomised, placebo-controlled study investigated whether metformin, compared to a placebo, could alleviate knee pain in individuals experiencing symptomatic knee osteoarthritis and who were living with overweight or obesity. Importantly, none of the participants had diabetes.

The research was conducted entirely within the community through telehealth consultations, making it accessible to participants across a range of locations. A total of 107 individuals (73 women and 34 men), with an average age of 60, were enrolled. Participants were randomised to receive either up to 2,000 mg of metformin daily or a placebo for six months.

Pain was assessed using a 0–100 scale, where 100 represents the worst imaginable pain. After six months, those in the metformin group reported an average reduction of 31.3 points, compared with an 18.9-point reduction in the placebo group—a difference considered to represent a moderate effect on pain.

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

A New, Affordable Treatment Option

Professor Flavia Cicuttini, lead researcher and Head of Monash University’s Musculoskeletal Unit as well as Head of Rheumatology at The Alfred Hospital, described the findings as highly promising. She highlighted that metformin could represent an affordable, novel approach to improving knee pain in people living with knee osteoarthritis and overweight or obesity.

Current treatments for knee OA primarily focus on lifestyle modifications such as exercise and weight management, interventions that many patients find challenging to maintain. Medications such as paracetamol, topical anti-inflammatory creams, and oral anti-inflammatory drugs are also used; however, they often provide limited benefit and may not be suitable for everyone due to safety concerns.

Notably, no new drugs for osteoarthritis have been approved in Australia since the late 1990s, with the approvals of Celebrex (celecoxib) and Vioxx (rofecoxib).

Professor Cicuttini emphasised that treatment options for managing knee pain in osteoarthritis remain scarce. She noted that this scarcity often drives both patients and their doctors to consider surgical options prematurely.

This has led to a growing issue both within Australia and internationally, with rising rates of knee replacements being performed for earlier stages of osteoarthritis. This trend is underpinned by the belief that effective non-surgical treatments are lacking and that prosthetic knees have long lifespans.

“At first glance this may seem reasonable, but it is a major problem because patient dissatisfaction with knee replacements is already high at between 20–30%, even when the operation is technically perfect,” Professor Cicuttini explained. “Dissatisfaction rates are highest when the operation is done for early knee OA.

“To go through the effort and cost of a big operation like a knee replacement, only to be unhappy with the results because of ongoing pain and symptoms, is definitely low-quality care. Doing a knee replacement earlier also increases the potential need for the procedure to be redone.

“This costs about 3.5 times as much, so about $70,000 compared to $20,000, and the results tend not to be as good as the first time. The best outcome for patients is to delay the knee replacements until it is absolutely needed.”

How Metformin Could Change Knee OA Care

Professor Cicuttini noted that metformin could now offer general practitioners (GPs) an alternative strategy to recommend alongside lifestyle measures such as weight management and increasing physical activity.

“Metformin works in a number of ways on the knee, including affecting low-grade inflammation and other metabolic pathways that are important in knee OA,” she said. “It is a different way to treat knee OA pain.

“GPs are very familiar with metformin, which is a low-cost, safe medication. 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. If people on metformin have less knee pain and are able to do more physical activity, then knee replacements can wait.”

The fact that metformin is already well known to GPs, affordable, and has a strong safety profile strengthens its potential as an adjunct therapy. Furthermore, if individuals experience reduced pain and can be more active, this may lead to additional benefits in joint health, functional capacity, and overall wellbeing.

Next Steps: Integrating Metformin into Knee OA Management

Professor Cicuttini and her team are now collaborating with patients, GPs, orthopaedic surgeons, and other healthcare professionals to explore how metformin can be incorporated into clinical care pathways for knee OA. The aim is to enhance patient outcomes and more effectively target surgical interventions when they are truly necessary.

Metformin could be prescribed ‘off label’ for this purpose, following thorough discussions between patients and their healthcare providers. This approach would allow for careful consideration of individual circumstances and potential benefits.

“Metformin is safe and well tolerated,” Professor Cicuttini stated. “It is used safely in other non-diabetes conditions such as polycystic ovarian syndrome. Metformin could be provided simply and safely using a telehealth approach, as we did in our study, meaning that it could be provided across the community, including in regional and remote areas.”

The study represents an important step forward in addressing the unmet needs of people living with knee osteoarthritis and overweight or obesity, offering a promising, accessible solution that may improve quality of life and reduce the reliance on invasive surgeries.