A common diabetes drug can reduce the pain of people with knee osteoarthritis and overweight or obesity, possibly delaying the need for knee replacements, Monash University-led research has found.

Metformin, which is commonly prescribed to treat type 2 diabetes, reduced knee arthritis pain over six months in a clinical trial published in JAMA.

The randomized clinical trial looked at whether metformin, compared to a placebo, reduced knee pain in patients with symptomatic knee osteoarthritis (knee OA) and overweight or obesity.

The research was performed entirely as a community-based study using telehealth. Some of the 107 participants with pain from knee osteoarthritis (73 women and 34 men), who had a mean age of 60, took up to 2000 mg of metformin daily for six months. Others took the placebo. None had diabetes.

Knee pain was measured on a 0-100 scale, with 100 being the worst. The metformin group reported a 31.3 point reduction in pain after six months, compared to 18.9 for the placebo group. This was considered 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 found. “Because of the modest sample size, confirmation in a larger clinical trial is warranted.”

Lead researcher Professor Flavia Cicuttini, who heads Monash University’s Musculoskeletal Unit and is The Alfred’s Head of Rheumatology, said the results showed that metformin was a potentially new and affordable way to improve knee pain in those with knee OA and overweight or obesity.

Knee OA treatments include lifestyle approaches such as exercise and weight loss, which patients often find difficult, and medications such as paracetamol, topical anti-inflammatory creams and oral anti-inflammatory medications which have small benefits and may be unsuitable for some patients for safety reasons.

No new OA drugs have been approved in Australia since Celebrex (celecoxib) and Vioxx (rofecoxib) in the late 1990s.

Professor Cicuttini said effective treatments that improved knee pain in osteoarthritis were limited. She said this led some patients and their doctors to seek alternative treatments including surgery.

This resulted in major problems managing knee OA in Australia and internationally, including an increase in the rate of knee replacements performed for earlier stages of OA. This was based on the idea that effective treatments for knee OA were limited and that knee replacements lasted a long time

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 per cent, even when the operation is technically perfect. 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.”

Professor Flavia Cicuttini, Lead Researcher

Professor Cicuttini said metformin now provided GPs an alternative they could offer patients in addition to managing weight and increasing 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.”

Professor Cicuttini and her colleagues are now working with consumers, GPs, orthopaedic surgeons and other healthcare professionals to introduce metformin into the knee OA management pathway in order to improve patient outcomes and potentially better target knee replacements. Metformin could be used ‘off label’ after discussions between patients and their doctor.

“Metformin is safe and well tolerated,” she said. “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.”

This research was supported by the National Health and Medical Research Council (NHMRC).