Metformin Reduces Knee Pain in Patients With Osteoarthritis and Overweight or Obesity

A randomized, double-blind, placebo-controlled trial has found that metformin significantly reduced knee pain in individuals with symptomatic knee osteoarthritis and overweight or obesity over a 6-month period. The findings support the potential role of metformin as a therapeutic option in this patient population.

The study enrolled 107 adults (mean age, 58.8 years; 68% women) with knee pain for at least 6 months, a body mass index (BMI) of 25 or higher, and a pain score greater than 40 mm on a 100-mm visual analog scale (VAS). Participants were randomized to receive either 2000 mg/day of oral metformin (n=54) or placebo (n=53). The primary outcome was change in knee pain on the VAS at 6 months, with a minimum clinically important difference defined as 15 mm.

At 6 months, the metformin group showed a mean pain reduction of 31.3 mm, compared to 18.9 mm in the placebo group. The between-group difference was –11.4 mm (95% CI, –20.1 to –2.6 mm; P = .01), with an effect size of 0.43 (95% CI, 0.02 to 0.83).

“These results support use of metformin for treatment of symptomatic knee osteoarthritis in people with overweight or obesity,” the authors concluded.

Adverse events were mild and included diarrhea (15% in the metformin group vs 8% in placebo) and abdominal discomfort (13% vs 9%, respectively).

While the sample size was modest and 82% of participants completed the trial, the findings align with preclinical evidence suggesting anti-inflammatory and cartilage-preserving effects of metformin.

The authors noted, “Confirmation in a larger clinical trial is warranted,” but the results offer practicing rheumatologists a potential new direction for pain management in knee osteoarthritis among patients with metabolic comorbidities.

Reference
Pan F, Wang Y, Lim YZ, et al. Metformin for knee osteoarthritis in patients with overweight or obesity: a randomized clinical trial. JAMA. 2025;333(20):1804-1812. doi:10.1001/jama.2025.3471