Real-World Impact of SGLT2 Inhibitors on Systemic Inflammation in Type 2 Diabetes: A Composite Biomarker-Based Evaluation

Abstract

Background: Chronic low-grade inflammation is increasingly recognized as a key contributor to the pathophysiology and complications of type 2 diabetes mellitus (T2DM). Although sodium-glucose co-transporter 2 (SGLT2) inhibitors offer established metabolic and cardiovascular benefits, their real-world impact on systemic inflammation remains unclear. In this study, we investigated the effects of SGLT2 inhibitor therapy on composite inflammation indices over six months in patients with T2DM and explored the differences across clinical subgroups and drug types. Methods: In this retrospective observational study, 163 adults with T2DM who were prescribed either empagliflozin or dapagliflozin were followed up for six months. Inflammatory burden was assessed using the pan-immune-inflammation value (PIV) and systemic immune-inflammation index (SII), which were calculated from the complete blood count parameters. Paired comparisons were performed using Wilcoxon signed-rank tests, and subgroup differences in ΔPIV and ΔSII were analyzed using the Mann–Whitney U-test. Results: At the sixth month, significant reductions were observed in both PIV (335.0 ± 287.4 to 282.6 ± 189.3; p=0.014) and SII (579.1 ± 332.8 to 496.0 ± 224.0; p<0.001). Empagliflozin led to greater improvements in ΔPIV (p=0.011) and ΔSII (p<0.001) than those with dapagliflozin. Subgroup analysis revealed that patients aged ≥55 years and those with a baseline SII >600 exhibited the most pronounced reductions in inflammatory indices. No significant differences were observed according to sex, BMI, or smoking status of the patients. Conclusion: SGLT2 inhibitors significantly reduce the systemic inflammatory burden in patients with T2DM, with empagliflozin demonstrating superior anti-inflammatory efficacy. The benefits are particularly evident in individuals with elevated baseline inflammation and older age, supporting the integration of inflammation-based biomarkers, such as PIV and SII, into future personalized therapeutic approaches.

Keywords

• SGLT2 inhibitors
• Systemic inflammation
• Type 2 diabetes mellitus
• PIV
• SII
• Inflammatory biomarkers

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