SGLT2 Inhibitors Are Associated With Suppression of the Sema3A/NRP1/Plexin-A1 Signaling Axis in Postmenopausal Women With Type 2 Diabetes: Evidence From Propensity Score-Matched Analysis


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Erarslan S., Bora B. C.

JOURNAL OF DIABETES, vol.18, no.9, pp.1-2, 2026 (SCI-Expanded, Scopus)

  • Publication Type: Article / Editorial Material
  • Volume: 18 Issue: 9
  • Publication Date: 2026
  • Doi Number: 10.1111/1753-0407.70262
  • Journal Name: JOURNAL OF DIABETES
  • Journal Indexes: Academic Search Ultimate (EBSCO), Biomedical Reference Collection: Corporate Edition (EBSCO), Health Research Premium Collection (ProQuest), Scopus, Science Citation Index Expanded (SCI-EXPANDED), EMBASE, MEDLINE, Directory of Open Access Journals
  • Page Numbers: pp.1-2
  • Open Archive Collection: AVESIS Open Access Collection
  • Kütahya Health Sciences University Affiliated: Yes

Abstract

Propensity score-matched comparison of 23 SGLT2 inhibitor users and 23 non-users revealed that SGLT2 inhibitor use was associated with significantly lower Neuropilin-1 (NRP1) levels (74.25 vs. 87.61 ng/mL; p = 0.015) and a higher Sema3A/NRP1 ratio (0.14 vs. 0.12; p = 0.006), indicating functional impairment of the Sema3A/NRP1/Plexin-A1 bone signaling axis with compensatory Sema3A upregulation. Classical bone turnover markers (P1NP, CTX, coupling index) and DXA-derived BMD did not significantly differ between groups. These findings suggest that SGLT2 inhibitors may perturb the Sema3A/NRP1/Plexin-A1 axis before detectable changes in conventional markers, offering a novel mechanistic perspective to explain the inconsistency between existing meta-analyses on SGLT2 inhibitor bone safety.