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

Abstract

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-α [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 reduces CRP level significantly in T2D patients compared to other inflammatory markers.

The effect of metformin on influenza vaccine responses in nondiabetic older adults: a pilot trial

“…Metformin can decrease various markers of inflammation in diabetics and other disease settings, however the effect of metformin on systemic inflammation in healthy, non-prediabetic and nondiabetic older adults has not been studied in depth. Metformin has previously been shown to decrease circulating levels of CRP, IL-6, and TNF-α in patients with type 2 diabetes [ 81 ], however this finding was not replicated in our subjects who were nondiabetic and nonprediabetic. It is likely that since our subjects were quite healthy with very limited co-morbidities and frailty levels that metformin did not have a measurable effect on circulating inflammatory levels.…”

Metformin use is associated with a decrease in the risk of hospitalization and mortality in COVID‐19 patients with diabetes: A population‐based study in Lombardy

“…Furthermore, metformin inhibits TNF‐α–dependent NF‐κB inflammatory signalling, leading to decreased secretion of inflammatory cytokines like CXCL1, CXCL2, IL‐1β, and IL‐6 8 . Consistent with this, metformin has been shown to reduce subclinical inflammation (measured by the neutrophil to lymphocyte ratio [NLR]) and C‐reactive protein concentrations in T2D 8,24,25 . In accordance with these anti‐inflammatory effects, preadmission metformin use was associated with reduced mortality among medical and surgical intensive care patients with T2D 26 .…”

“…21 For these reasons, it is an ideal therapy for randomized controlled trials (RCTs) in the face of the ongoing COVID- ) and C-reactive protein concentrations in T2D. 8,24,25 In accordance with these anti-inflammatory effects, preadmission metformin use was associated with reduced mortality among medical and surgical intensive care patients with T2D. 26 The This study also suffers the limitations characteristic of administrative databases.…”

Comparison of inflammatory markers in type 2 diabetic patients treated with empagliflozin, metformin, and sulfonylurea

“…According to the US Diabetes Prevention Study, this drug results in diminishing CRP levels in individuals suffering from impaired glucose tolerance (20). The results of recent research have suggested the anti-inflammatory effect of metformin on patients with T2D (21). Some researchers, in a systematic review, reported CRP as the highest effect of metformin on lowering inflammatory factor levels in type 2 diabetic individuals, thus the value of this factor diminishes significantly (21).…”