medwireNews: Treatment with the diabetes medication metformin for 6 months significantly reduces knee pain in patients with symptomatic knee osteoarthritis (OA) who have overweight or obesity, according to findings from a randomized clinical trial.
Reporting the findings in JAMA, Flavia Cicuttini, from Monash University in Melbourne, Victoria, Australia, and colleagues write that treatment with metformin 2000 mg/day for 6 months had a “moderate and statistically significant effect on knee pain reduction compared with placebo," although they caution that due to "the modest sample size, confirmation in a larger clinical trial is warranted."
Conducted remotely due to COVID-19 restrictions, the double-blind, placebo-controlled trial recruited and monitored 107 participants via telemedicine between June 2021 and February 2024. The participants (mean age 58.8 years; 68% women) had symptomatic knee OA for at least 6 months, a BMI of 25 kg/m² or above, and baseline knee pain scores greater than 40 mm on a 100-mm visual analog scale (VAS), where 0 mm indicates "no pain" and 100 mm represents the "worst imaginable pain."
The presence of knee OA was diagnosed according to the American College of Rheumatology criteria adapted specifically for telemedicine. Physical examinations were not conducted; instead, participants received telemedicine guidance on performing their own knee assessments, reporting symptoms such as knee crepitus, tenderness, and warmth. Bony enlargement, the authors note, was not evaluated due to its subjective nature.
A total of 54 patients received metformin, at a daily dose of 500 mg, increasing up to 2000 mg over a 6-week period, for 6 months, while 53 received placebo.
The index knee selected for assessment was determined by the higher pain severity, the severity of radiographic osteoarthritis, or, if these were equal, the participant's dominant knee.
At the study’s 6-month conclusion, 82% of participants had completed the trial. Those receiving metformin had a significant, 11.4 mm greater reduction in knee pain, after adjusting for differences at baseline, with mean VAS scores improving by 31.4 mm, from 60.2 mm at baseline to 28.8 mm at 6 months. This compared with an 18.9 mm improvement in the placebo group, from 58.5 mm to 39.6 mm.
However, the authors acknowledge that “the 15-mm [minimum clinically important difference] used to calculate statistical power was not obtained,” noting therefore that “the results may not be clinically meaningful.” They add that “[t]he current study did not identify a benefit of metformin at [the] 3-month follow-up.”
Secondary outcomes that favored metformin included significant improvements on the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), a scale assessing knee pain, stiffness, and physical function. Metformin led to significantly greater improvements on each of the subscales, with adjusted mean reductions versus placebo of 42.4 points, 23.0 points, and 179.8 points, respectively.
The trial reported 41 adverse events – 25 events in 16 metformin-treated participants and 16 events in 10 placebo-treated participants. These were primarily gastrointestinal issues such as diarrhea (15 vs 8%) and abdominal discomfort (13 vs 9%) and were mild to moderate in severity.
The researchers acknowledge limitations to the study, including 19 (18%) patients being lost to follow-up, and reliance on participant self-reporting for medication adherence – assessed via telemedicine and returned pill counts – with adherence rates of 82% in the metformin group and 79% in the placebo group. However, with only 38% of participants returning pill counts, this may be an overestimate, they say.
Nevertheless, based on the 6-month follow-up, the authors conclude that the “results support use of metformin for treatment of symptomatic knee OA in people with overweight or obesity.”
medwireNews is an independent medical news service provided by Springer Healthcare Ltd. © 2025 Springer Healthcare Ltd, part of the Springer Nature Group
