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Review
. 2022 Nov 11:13:1045235.
doi: 10.3389/fphar.2022.1045235. eCollection 2022.

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

Dongmei Wang  1 , Jieying Liu  1   2 , Ling Zhong  1 , Shunhua Li  1 , Liyuan Zhou  1 , Qian Zhang  1 , Ming Li  1 , Xinhua Xiao  1
Affiliations
Review

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

Dongmei Wang et al. Front Pharmacol. .

Abstract

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.

Keywords: SGLT2 inhibitor; diabetes; inflammation; meta-analysis; randomized controlled trial.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
The process of study selection.
FIGURE 2
FIGURE 2
Summary of risk of bias using the Cochrane risk of bias tool.
FIGURE 3
FIGURE 3
Forest plot of the effects of SGLT2 inhibitors on C-reactive protein.
FIGURE 4
FIGURE 4
Forest plot of the effects of SGLT2 inhibitors on tumor necrosis factor-alpha.
FIGURE 5
FIGURE 5
Forest plot of the effects of SGLT2 inhibitors on interleukin-6.
FIGURE 6
FIGURE 6
Forest plot of the effects of SGLT2 inhibitors on adiponectin.
FIGURE 7
FIGURE 7
Forest plot of the effects of SGLT2 inhibitors on leptin.
FIGURE 8
FIGURE 8
Forest plot of the effects of SGLT2 inhibitors on ferritin.
FIGURE 9
FIGURE 9
Forest plot of the effects of SGLT2 inhibitors on plasminogen activator inhibitor-1.
See this image and copyright information in PMC

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