AUTHOR=Wang Dongmei , Liu Jieying , Zhong Ling , Li Shunhua , Zhou Liyuan , Zhang Qian , Li Ming , Xiao Xinhua 

TITLE=The effect of sodium-glucose cotransporter 2 inhibitors on biomarkers of inflammation: A systematic review and meta-analysis of randomized controlled trials

JOURNAL=Frontiers in Pharmacology

VOLUME=13

YEAR=2022

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2022.1045235

DOI=10.3389/fphar.2022.1045235

ISSN=1663-9812

ABSTRACT=<p><bold>Aims:</bold> Inflammatory biomarkers may play vital roles in the pathophysiology of diabetes and diabetic cardiorenal complications. Sodium-glucose cotransporter-2 (SGLT2) inhibitors have a potential cardiovascular and renal protective effect in type 2 diabetes. The aim of this meta-analysis was to quantify the effects of SGLT2 inhibitors on biomarkers of inflammation in randomized controlled trials (RCTs).</p><p><bold>Methods:</bold> PubMed, Cochrane Library, EMBASE, and Web of Science were searched for eligible RCTs of adults with type 2 diabetes (T2D) with no time limit (updated to 12 October 2022). The biomarkers selected included C-reactive protein (CRP), interleukin-6, tumor necrosis factor-alpha, leptin, adiponectin, ferritin, plasminogen activator inhibitor (PAI)-1, and vascular cell adhesion molecule-1. Data were analyzed using a random-effect model in Review Manager 5.4.</p><p><bold>Results:</bold> Thirty-four studies with 6,261 patients (68.6% male) were eligible for this meta-analysis. The mean age of the participants was 62.57(±11.13) years old, and the median treatment duration length with follow-up was 24 weeks. Generally, the included trials were of good methodological quality. The meta-analysis revealed that ferritin levels were significantly reduced in SGLT2 inhibitor treatment groups <italic>versus</italic> placebo or standard diabetes therapies (SMD: −1.21; 95% CI: −1.91, −0.52, <italic>p</italic> &lt; 0.001). The effects of CRP (SMD: 0.25; 95% CI: −0.47, −0.03, <italic>p</italic> = 0.02) and leptin (SMD: −0.22; 95% CI: −0.43, −0.01, <italic>p</italic> = 0.04) were reduced, and the effects of adiponectin were improved (SMD: 0.28; 95% CI: 0.15, 0.41, <italic>p</italic> &lt; 0.001) in placebo-controlled studies. PAI-1 levels were significantly reduced in studies controlled for diabetes therapies (SMD: −0.38; 95% CI: −0.61, −0.15, <italic>p</italic> = 0.001).</p><p><bold>Conclusion:</bold> This analysis provides strong evidence supporting anti-inflammatory effects of SGLT2 inhibitors in T2D subjects. The mechanisms and possible targets for the inflammation reducing and cardiorenal protective properties of SGLT2 inhibitors remain to be explored.</p>