Aims: 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). Methods: 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. Results: 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 versus placebo or standard diabetes
therapies (SMD: -1.21; 95% CI: -1.91, -0.52, p < 0.001). The effects of CRP (SMD: 0.25; 95% CI: -0.47, -0.03, p = 0.02) and
leptin (SMD: -0.22; 95% CI: -0.43, -0.01, p = 0.04) were reduced, and the effects of
adiponectin were improved (SMD: 0.28; 95% CI: 0.15, 0.41, p < 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, p = 0.001). Conclusion: 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.