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Introduction <p>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.</p> Methods <p>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&#xa0;kg/m<sup>2</sup> 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.</p> Results <p>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; I<sup>2</sup> = 95%). Sensitivity analysis excluding an outlier study produced a consistent effect (SMD: − 0.54; 95% CI: − 0.74 to − 0.33; I<sup>2</sup> = 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; I<sup>2</sup> = 0%), with moderate certainty due to imprecision.</p> Conclusions <p>Metformin provides clinically meaningful pain reduction in overweight/obese adults with knee OA but increases mild, non-serious gastrointestinal adverse events. These findings support metformin as a promising disease-modifying therapy for metabolically complex OA phenotypes; longer-duration trials with structural endpoints are warranted.</p>

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Metformin for knee osteoarthritis in overweight and obese adults: a systematic review and meta-analysis of efficacy, safety, and disease-modifying anti-inflammatory potential

  • 期刊论文

  • 发表日期：

    2026年4月27日

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  • Santenna Chenchula,
  • Krishna Chaitanya Amerneni,
  • R. Padmavathi,
  • K. Anitha,
  • Mohan Krishna Ghanta,
  • Shriraam Karunakaran,
  • Shubham Atal,
  • Sunil Kumar,
  • Pavani Saggurthi,
  • Shoibam Jenifa,
  • K. Mythili Bai,
  • Madhavrao Chavan,
  • Balakrishnan Sadasivam

摘要

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.

Conclusions

Metformin provides clinically meaningful pain reduction in overweight/obese adults with knee OA but increases mild, non-serious gastrointestinal adverse events. These findings support metformin as a promising disease-modifying therapy for metabolically complex OA phenotypes; longer-duration trials with structural endpoints are warranted.