The effect of sodium-glucose cotransporter-2 inhibitors on inflammatory biomarkers: A meta-analysis of randomized controlled trials

Diabetes Obes Metab. 2024 Jul;26(7):2706-2721. doi: 10.1111/dom.15586. Epub 2024 Apr 11.

Abstract

Aims: To conduct a meta-analysis of randomized controlled trials (RCTs) to assess the effect of sodium-glucose cotransporter-2 (SGLT2) inhibitors on inflammatory biomarkers.

Methods: Medline, Embase and the Cochrane Library were searched for RCTs investigating the effect of SGLT2 inhibitors on inflammatory biomarkers, adipokine profiles and insulin sensitivity.

Results: Thirty-eight RCTs were included (14 967 participants, 63.3% male, mean age 62 ± 8.6 years) with a median (interquartile range) follow-up of 16 (12-24) weeks. Meta-analysis showed that SGLT2 inhibitors significantly improved adiponectin, interleukin-6, tumour necrosis factor receptor-1 (vs. placebo alone: standardized mean difference [SMD] 0.34 [95% confidence interval {CI} 0.23, 0.45], mean difference [MD] -0.85 pg/mL [95% CI -1.32, -0.38], SMD -0.13 [95% CI -0.20, -0.06], respectively), leptin and homeostatic model assessment of insulin resistance index (vs.

Control: SMD -0.20 [95% CI -0.33, -0.07], MD -0.83 [95% CI -1.32, -0.33], respectively). There were no significant changes in C-reactive protein (CRP), tumour necrosis factor-α, plasminogen activator inhibitor-1, fibroblast growth factor-21 or monocyte chemoattractant protein-1.

Conclusions: Our analysis shows that SGLT2 inhibitors likely improve adipokine biomarkers and insulin sensitivity, but there is little evidence that SGLT2 inhibitors improve other inflammatory biomarkers including CRP.

Keywords: cardiovascular disease; dapagliflozin; empagliflozin; inflammation; mechanism of action; sodium‐glucose co‐transporter‐2 inhibitors.

Publication types

  • Meta-Analysis
  • Systematic Review

MeSH terms

  • Adipokines / blood
  • Adiponectin / blood
  • Aged
  • Biomarkers* / blood
  • C-Reactive Protein / analysis
  • C-Reactive Protein / metabolism
  • Diabetes Mellitus, Type 2* / blood
  • Diabetes Mellitus, Type 2* / drug therapy
  • Female
  • Humans
  • Inflammation* / blood
  • Insulin Resistance
  • Interleukin-6 / antagonists & inhibitors
  • Interleukin-6 / blood
  • Leptin / blood
  • Male
  • Middle Aged
  • Plasminogen Activator Inhibitor 1 / blood
  • Randomized Controlled Trials as Topic
  • Sodium-Glucose Transporter 2 Inhibitors* / pharmacology
  • Sodium-Glucose Transporter 2 Inhibitors* / therapeutic use

Substances

  • Adipokines
  • Adiponectin
  • Biomarkers
  • C-Reactive Protein
  • Interleukin-6
  • Leptin
  • Plasminogen Activator Inhibitor 1
  • Sodium-Glucose Transporter 2 Inhibitors