Delaying knee replacements and improving patient outcomes may be possible with off-label metformin.
Patients with knee osteoarthritis may be able to delay surgery, and suffer less pain and stiffness, thanks to a cheap and safe medication, according to new research from Monash University.
The researchers found that taking 2000mg of metformin per day for six months led to a 65% greater reduction in pain compared to placebo.
Pain was assessed using the 0-100 VAS scale in a randomised double-blind trial of 107 Victorian adults (73 women and 34 men) with knee osteoarthritis. The treatment group showed a 31.3-point reduction in pain after six months compared to 18.9 for the placebo group.
Metformin also significantly improved pain on the 500-point WOMAC scale (−113.9 with metformin vs −68.2 with placebo), stiffness (−56.9 vs −26.7 on a 200-point scale) and function (−426.1 vs −221.7 on a 1700-point scale).
Lead researcher Professor Flavia Cicuttini, head of rheumatology at the Alfred Hospital, said metformin could be prescribed off label to provide an alternative to the limited treatment options available for knee OA and to delay surgery.
“If people on metformin have less knee pain and are able to do more physical activity, then knee replacements can wait,” she told media.
She said due to the high rates of patient dissatisfaction, ongoing pain and symptoms often experienced after surgery, even when the operation was technically perfect, the best outcome for patients was to delay knee replacement until absolutely necessary.
“Doing a knee replacement earlier also increases the potential need for the procedure to be redone,” Professor Cicuttini said.
“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.”
The most common adverse events in the study were diarrhea (15% in the metformin group and 8% in the placebo group) and abdominal discomfort (13% in the metformin group and 9% in the placebo group).
“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.”
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All participants were overweight or obese, with a BMI of 25 or higher, and had experienced knee pain from osteoarthritis for a minimum of six months. None had diabetes.
“The current study did not identify a benefit of metformin at three-month follow-up but identified a significant benefit at six-month follow-up. The time course for any potential benefit of metformin in knee OA is unknown,” Professor Cicuttini and colleagues wrote in JAMA.
“The pleiotropic mechanisms of metformin, including its effects on inflammation and glucose and lipid metabolism, suggest that the benefits may take longer than three months in humans to manifest.”
That may explain why the benefits were only found at the six-month mark, they said.
