Metformin May Ease Knee Pain in Overweight Osteoarthritis Patients: Randomized Trial Suggests Modest Benefit

Preclinical studies and early human evidence have indicated that metformin, a widely used first-line treatment for type 2 diabetes, may help reduce inflammation, preserve cartilage, and alleviate knee pain in individuals with knee osteoarthritis. Building on these findings, Feng Pan, School of Public Health and Preventive Medicine, Monash University, Melbourne, Victoria, Australia, and colleagues conducted a recent clinical trial to assess the effects of metformin on knee pain after six months in people experiencing symptomatic knee osteoarthritis who were also overweight or obese.

For this purpose, the researchers conducted a community-based, randomized, double-blind, placebo-controlled clinical trial using telemedicine to recruit and monitor participants remotely. Adults with knee pain lasting over six months, a pain score above 40 mm on a 100-mm visual analog scale (VAS), and a body mass index of 25 or higher were enrolled through local and social media in Victoria, Australia, between June 2021 and August 2023. Participants were randomly assigned to receive either 2000 mg/day of oral metformin or a matching placebo for six months. The primary outcome was the change in knee pain on the VAS at six months.

The key findings of the study were as follows:

• Out of 225 individuals assessed, 107 participants (48%) were randomized to receive either metformin or placebo. The average age of participants was 58.8 years, and 68% were women.
• A total of 88 participants (82%) completed the six-month trial.
• At six months, the average reduction in knee pain on the VAS was 31.3 mm in the metformin group and 18.9 mm in the placebo group.
• The between-group difference in pain reduction was 11.4 mm.
• The effect size was 0.43, indicating a moderate benefit.
• The most commonly reported adverse events were diarrhea (15% in the metformin group vs 8% in the placebo group) and abdominal discomfort (13% vs 9%).

The study highlights that a six-month course of metformin at 2000 mg/day offers a moderate yet statistically significant reduction in knee pain among overweight or obese individuals with symptomatic knee osteoarthritis. These findings suggest that metformin could be a promising treatment option in this patient population. However, the authors emphasize the need for larger-scale clinical trials to validate and strengthen these observations, given the modest sample size of the current trial.

Reference:

Pan F, Wang Y, Lim YZ, et al. Metformin for Knee Osteoarthritis in Patients With Overweight or Obesity: A Randomized Clinical Trial. JAMA. Published online April 24, 2025. doi:10.1001/jama.2025.3471