Effect of Metformin on Circulating Levels of Inflammatory Markers in Patients With Type 2 Diabetes: A Systematic Review and Meta-analysis of Randomized Controlled Trials

Background: Emerging evidence indicates that metformin has anti-inflammatory effect; however, the results differ concerning randomized controlled trails of the effect of metformin on inflammatory markers in type 2 diabetes (T2D) patients. Objective: This study reassessed the data on the effect of metformin treatment on inflammatory markers in T2D patients through a systematic review and meta-analysis. Methods: A systematic search was performed in the PubMed, ISI Web of Science, EMBASE, Cochrane Library and Scopus databases to collect relevant published data up to September 2020. Data of each study was combined using random-effects model. Subgroup analysis was performed based on subgroups of the treatment duration, dose and target population. Results: Thirteen RCTs including 1776 participants with T2D were analyzed. Although CRP levels significantly decreased [SMD: -0.76 mg/L; 95% CI (-1.48, -0.049); P = 0.036] in patients with T2D following metformin treatment, circulating levels of TNF-alpha [SMD: -0.17 pg/mL; 95% CI (-0.55, 0.20); P = 0.37] and IL-6 [SMD: -0.06 pg/mL; 95% CI (-0.38, 0.25); P = 0.69] were insignificant after metformin treatment. Compared to treatment duration of less than 24 weeks, longer treatment duration (more than 24 weeks) was associated with reduced level of CRP. Relevance to Patient Care and Clinical Practice: Based on available evidence from RCTs in this meta-analysis, metformin decreased CRP level. However, strategies for the treatment of inflammation should focus on metformin in patients with T2D. Conclusion: The present study evidences that therapy with metformin can reduce CRP level significantly in T2D patients compared to other inflammatory markers.