Metformin for knee osteoarthritis in overweight and obese adults: a systematic review and meta-analysis of efficacy, safety, and disease-modifying anti-inflammatory potential
Abstract
Introduction: Knee osteoarthritis (OA) is a degenerative joint disease involving progressive cartilage loss, subchondral bone remodelling, and inflammation. This systematic review and meta-analysis aimed to assess the efficacy and safety of metformin in reducing knee pain and adverse events among overweight and obese adults with symptomatic knee OA.
Methods: We systematically searched PubMed, Scopus, and CENTRAL from inception to August 2025. Eligible randomised controlled trials (RCTs) compared oral metformin with placebo or standard care in adults with BMI ≥ 25 kg/m2 and symptomatic knee OA. Primary outcomes were pain reduction (standardised mean difference) and gastrointestinal (GI) adverse events (risk ratio). Risk of bias was assessed using the Cochrane ROB 2 tool, publication bias using the Doi plot and LFK index, and evidence certainty using the GRADE-pro approach.
Results: Seven studies (n = 1237) were included: six RCTs and one observational study. Meta-analysis included only RCTs. Metformin significantly reduced knee pain compared with controls (SMD: - 0.42; 95% CI: - 0.62 to - 0.21; I2 = 95%). Sensitivity analysis excluding an outlier study produced a consistent effect (SMD: - 0.54; 95% CI: - 0.74 to - 0.33; I2 = 91%). Based on GRADE assessment, the certainty of evidence for pain reduction was high. Metformin increased the risk of mild, non-serious gastrointestinal adverse events (RR: 1.97; 95% CI: 1.06-3.67; I2 = 0%), with moderate certainty due to imprecision.…
How strong is the evidence?
Evidence Hub reads this as a meta-analysis, done in people. Its evidence level is 1 of 5 (Highest · pooled evidence). Pooled evidence from several studies sits at the top of the evidence pyramid. Reported size: 1,237 participants or records.
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