June 2025
Potential role for metformin in reducing pain in patients with knee osteoarthritis
By Dr Emily Lathlean MB BS, FRACGP
A randomised clinical trial by Australian researchers has found metformin to be helpful in reducing osteoarthritis-related knee pain in patients with overweight or obesity.
In the trial, published in JAMA, 107 patients with a body mass index of 25 kg/m2 or higher and aged over 40 years were randomised and assigned to receive metformin (2000 mg/day) or placebo. At baseline, participants had experienced knee pain for six months or longer and a pain score greater than 40 mm on a 100 mm visual analogue scale (VAS), with scores from 0 to 100, with 100 being the worst. Participants with diabetes requiring glucose-lowering therapy were among those excluded from the trial.
At six months, of the 88 participants who completed the trial, those taking metformin had a more significant change in VAS pain scores (-31.3 mm) compared with patients taking placebo (-18.9 mm).
The researchers acknowledged several limitations of the study, including its relatively small sample size and the remote nature of assessments in the study.
‘This trial suggests that the management of osteoarthritis may be benefited in those who are overweight and obese with the addition of metformin,’ said Professor David Hunter, Florance and Cope Chair of Rheumatology and Professor of Medicine at The University of Sydney, and Rheumatologist at Royal North Shore Hospital, Sydney. ‘This appears to be relatively safe.’
The most common adverse events were diarrhoea (affecting 15% of participants in the metformin group and 8% in the placebo group) and abdominal discomfort (affecting 13% of participants in the metformin group and 9% in the placebo group).
‘As a generic [medication], [metformin] is relatively inexpensive,’ Professor Hunter said. ‘Its effects may take a while to be found – with this trial suggesting there was no benefit at three months whereas there was at six months.’
Professor Hunter commented on the potential mechanisms of action of metformin in this ‘off-label’ context in patients without diabetes.
‘A large proportion of people with osteoarthritis have metabolic syndrome, and this leads to an increased risk of disease as well as increased symptoms and risk of progression,’ Professor Hunter said. ‘Metformin likely has a multitude of roles, including its effects on glucose and lipid metabolism, as well as direct effects on inflammation that may have beneficial effects on joint health.’
However, Professor Hunter cautioned that the mechanism required further examination and that more research was needed before its routine use in this context could be widely recommended.
‘It would be helpful for this result to be replicated,’ said Professor Hunter. ‘The trial will definitely be considered in the upcoming revision of the RACGP [osteoarthritis] guidelines, but at this point it’s premature to say that [metformin] will be recommended.’