Effects of Sodium-Glucose Cotransporter-2 Inhibitors on Inflammatory Biomarkers: A Systematic Review and Meta-Analysis.

BACKGROUND AND AIMS: Sodium-glucose cotransporter-2 inhibitors (SGLT2is) improve cardiovascular and kidney outcomes, but their effects on circulating inflammatory biomarkers remain uncertain. We systematically reviewed randomized evidence on the effects of SGLT2is on peripheral-blood inflammatory biomarkers.

METHODS

PubMed, Ovid MEDLINE, Scopus, Web of Science, and the Cochrane Library were searched from database inception to January 15, 2026. Randomized controlled trials enrolling adults and reporting at least one prespecified circulating inflammatory biomarker were included. Random-effects meta-analyses used restricted maximum likelihood estimation with Hartung-Knapp-adjusted inference. Eligible studies without effect estimates and variance data compatible with quantitative pooling were synthesized narratively.

RESULTS

Forty-seven randomized trials reported across 48 publications met the eligibility criteria; 38 trials contributed to at least one quantitative synthesis and 9 were synthesized narratively only. SGLT2i therapy did not significantly reduce CRP/hsCRP (MD -1.13 mg/L; 95% CI -2.31 to 0.05; I2 = 92.6%) or IL-6 (MD -1.53 pg/mL; 95% CI -3.69 to 0.64; I2 = 89.8%). TNF-α showed a small reduction in the primary analysis (SMD -0.39; 95% CI -0.71 to -0.07; I2 = 73.7%), although its prediction interval crossed the null. Narrative findings were mixed.

CONCLUSIONS

SGLT2i therapy did not show statistically significant reductions in CRP/hsCRP or IL-6, while the primary TNF-α finding was modest although its prediction interval crossed the null. Substantial heterogeneity, wide prediction intervals, and very low certainty of evidence limit clinical interpretation.

TRIAL REGISTRATION: PROSPERO number: CRD420261298312.