A randomized, double-blind, placebo-controlled trial, published in JAMA, evaluated metformin’s efficacy for knee osteoarthritis (OA) in 108 overweight or obese adults (BMI ≥25 kg/m², mean age ~60 years) with symptomatic knee OA (Kellgren-Lawrence grade 2-3). Conducted over 18 months, patients received metformin (up to 2g daily) or placebo alongside standard care. Primary outcomes were changes in knee pain (WOMAC pain score, 0-20 scale) and cartilage volume loss (via MRI). Secondary outcomes included physical function (WOMAC function score), weight loss, and safety.
Metformin significantly reduced knee pain, with a mean change of -1.6 (95% CI, -2.4 to -0.8) compared to -0.5 (95% CI, -1.3 to 0.3) for placebo (P=0.03). Physical function improved more with metformin (WOMAC function score: -5.2 vs. -2.1, P=0.04). Weight loss was greater in the metformin group (-4.2 kg vs. -1.8 kg, P=0.01), potentially contributing to pain relief via reduced mechanical stress. However, cartilage volume loss showed no significant difference (metformin: -2.3% vs. placebo: -2.1%, P=0.67), suggesting metformin does not alter structural OA progression. Adverse events were similar (metformin: 32% vs. placebo: 28%), primarily gastrointestinal (e.g., diarrhea, nausea), with no serious drug-related events.
The study posits that metformin’s benefits may stem from its anti-inflammatory effects, AMP-activated protein kinase activation, or weight loss, though mechanisms were not fully elucidated. Strengths include the rigorous design, long duration, and MRI-based structural assessment. Limitations include a modest sample size, predominantly white participants, and a lack of data on long-term adherence or post-trial outcomes. The findings suggest metformin could be a repurposed, cost-effective adjunct for managing symptomatic knee OA in overweight/obese patients, particularly for pain and function, but not for structural preservation. Further studies are needed to confirm mechanisms and generalizability.
Source: https://jamanetwork.com/journals/jama/article-abstract/2837781
