Metformin hope for knee OA

4 minute read

Recent studies reveal how the widely used diabetes drug could be a new way to treat knee osteoarthritis.

Metformin may reduce the need for total knee replacements in patients with diabetes by slowing the progression of knee osteoarthritis, according to new research.  

The retrospective propensity-matched cohort study, published in Scientific Reports, used electronic records from Hong Kong’s public primary care database to measure the incidence of total knee replacements between 2011 and 2014. Around 93,000 diabetic patients aged 45 and over were included in the final cohort, with half taking metformin regularly and the other half not taking the drug at all. 

Despite the overall low occurrence of total knee replacements, researchers found that participants who regularly used metformin had almost a 20% reduction in the rate of total knee replacements compared to non-users (184 vs 222 respectively).  

Known for its benefits across a number of conditions, the study’s findings highlight metformin’s potential for modifying osteoarthritis and subsequently preventing long-term disability in diabetic patients. 

However, more research needs to be done to support its clinical application in this context, according to rheumatologist David Hunter, Professor of Medicine at the University of Sydney and co-author of study. 

Professor Hunter told Rheumatology Republic that other confounding factors outside of diabetes could have contributed to the rate of joint replacement among participants, and that the generalisability of the findings to primary care populations in other countries remained unclear. 

“Hopefully, the findings raise awareness that metabolic disease, particularly for people who have diabetes but also those with abnormal cholesterol lipids or systemic inflammation, raises the risk of both developing osteoarthritis and its progression.  

“But at the moment I don’t think we should categorically say that we should use metformin in people who have or are at risk of developing osteoarthritis, because I don’t think the data we have at this point is strong enough to support that,” he advised. 

Further research should focus on measuring whether metformin can modify osteoarthritis in people with metabolic risk factors, in order to prove that the drug on its own can be a disease-modifying therapy, said Professor Hunter. 

“From a clinical perspective, I actually think there are probably more facilitators than there are barriers to its use, because a lot of clinicians may not necessarily want to use some agents for treating osteoarthritis. Metformin is widely used, people are very familiar with it, it’s got a pretty well-known side-effect profile, it’s easy to access and cheap, so I think there’s a lot of positives here. 

“However, I’m not suggesting that we should be using metformin widely at this point. I think [clinicians] should recognise that the presence of comorbidities like diabetes and metabolic and lipid changes are incredibly common in osteoarthritis, and in an ideal world osteoarthritis should be managed aggressively, that’s the key message here.” 

The results of the study are consistent with findings of a systematic review, published in Osteoarthritis and Cartilage, examining the role of metformin in modifying osteoarthritis.  

Conducted by a team of researchers from Monash University and Melbourne’s Alfred Hospital, the review surveyed 10 pre-clinical and five human studies to find consistent evidence that metformin had a chondroprotective, immunomodulatory and pain-relieving effect on knee osteoarthritis. 

“The results of the review need to be confirmed in randomised trials, however, they [show] the potential for very significant benefit,” said Professor Flavia Cicuttini, Head of the Musculoskeletal Unit at Monash University and co-author of systematic review. 

Professor Cicuttini told Rheumatology Republic that, depending on the findings of further research, metformin could have a profound impact on the otherwise costly treatment of knee osteoarthritis, as it is a “low-cost, well-tolerated, easy-to-use medication that could be readily translated into clinical care.”  

Professor Cicuttini and her team are currently conducting a randomised placebo-controlled trial, assessing the impact of metformin in treating symptomatic knee osteoarthritis. 

Scientific Reports 2022, online 7 July 

Osteoarthritis and Cartilage 2022, online 17 May 

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