Metformin for Knee Osteoarthritis in Patients With Overweight or Obesity

Preclinical and preliminary human evidence suggests that metformin, a first-line treatment for type 2 diabetes, reduces inflammation, preserves cartilage, and improves knee pain in knee osteoarthritis.

To evaluate the effects of metformin on knee pain at 6 months in participants with symptomatic knee osteoarthritis and overweight or obesity. Design, Setting, and Participants: Community-based randomized, parallel-group, double-blind, placebo-controlled clinical trial that used telemedicine to recruit and follow up participants remotely. Individuals with knee pain for 6 months or longer, a pain score greater than 40 mm on a 100-mm visual analog scale (VAS), and body mass index of 25 or higher were recruited from the community through local and social media advertisements in Victoria, Australia, between June 16, 2021, and August 1, 2023. Final follow-up occurred on February 8, 2024. Interventions: Participants were randomly assigned to receive either oral metformin, 2000 mg/d (n = 54), or identical placebo (n = 53) for 6 months. Main Outcomes and Measures: The primary outcome was change in knee pain, measured using a 100-mm VAS (score range, 0-100; 100 = worst; minimum clinically important difference = 15) at 6 months.