Category: Orthopedics
Posted: 5/6/2025 by Brian Corwell, MD
(Updated: 5/24/2025)
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Metformin, most widely used for type 2 diabetes, has shown promising early results in several different health outcomes.
A recent study, published in JAMA, investigated whether metformin could reduce knee pain in patients with symptomatic knee OA who were overweight or obese.
This was a small double-blind, placebo-controlled clinical trial involving 107 participants.
Background: There is some evidence (both preclinical and preliminary human) that metformin can reduce cartilage degradation and increase chondrocyte viability.
Intervention: Participants received metformin 2000 mg/day (n=54), or identical placebo (n=53) for 6 months.
Mean age, 58.8 [SD, 9.5] years. 68% female.
Patients had symptomatic radiologic knee OA and a body mass index > 25.
Adverse effects: Diarrhea (8 [15%] in the metformin group and 4 [8%] in the placebo group) and abdominal discomfort (7 [13%] in the metformin group and 5 [9%] in the placebo group).
Despite this, there were high levels of medication adherence.
The study found significant differences in primary and secondary outcome measures: Knee pain, stiffness and function.
There was some weight loss in both groups (mean change, 4 lbs in the metformin group and 2.6 lbs in the placebo group). Unlikely to explain outcome differences.
Conclusion: In patients with symptomatic knee osteoarthritis who were overweight or obese, metformin, had a moderate and statistically significant reduction in knee pain compared with placebo. Because of the small sample size, confirmation in a larger clinical trial is warranted.
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.
