The effect of sodium/glucose cotransporter 2 (SGLT2) inhibition on the urinary proteome

PLoS One. 2017 Oct 30;12(10):e0186910. doi: 10.1371/journal.pone.0186910. eCollection 2017.


Treatment with empagliflozin, an inhibitor of the sodium/glucose cotransporter 2 (SGLT2), is associated with slower progression of diabetic kidney disease. In this analysis, we explored the hypothesis that empagliflozin may have an impact on urinary peptides associated with chronic kidney disease (CKD). In this post-hoc, exploratory analysis, we investigated urine samples obtained from 40 patients with uncomplicated type 1 diabetes (T1D) before and after treatment with empagliflozin for 8 weeks to for significant post-therapy changes in urinary peptides. We further assessed the association of these changes with CKD in an independent cohort, and with a previously established urinary proteomic panel, termed CKD273. 107 individual peptides significantly changed after treatment. The majority of the empagliflozin-induced changes were in the direction of "CKD absent" when compare to patients with CKD and controls. A classifier consisting of these 107 peptides scored significantly different in controls, in comparison to CKD patients. However, empagliflozin did not impact the CKD273 classifier. Our data indicate that empagliflozin induces multiple significant changes in the urinary proteomic markers such as mucin and clusterin. The relationship between empagliflozin-induced proteomic changes and clinical outcomes merits further investigation.

MeSH terms

  • Humans
  • Proteome / antagonists & inhibitors*
  • Sodium-Glucose Transporter 2
  • Sodium-Glucose Transporter 2 Inhibitors*
  • Urine


  • Proteome
  • SLC5A2 protein, human
  • Sodium-Glucose Transporter 2
  • Sodium-Glucose Transporter 2 Inhibitors

Grants and funding

DC has received consulting fees or speaking honorarium or both from Janssen, Boehringer Ingelheim-Eli Lilly, AstraZeneca, Merck, Sanofi, and his institution has received operating funding from Janssen, Boehringer Ingelheim-Eli Lilly, AstraZeneca, Merck. HM is the co-founder and co-owner of Mosaiques Diagnostics. BAP has received fees for continuing medical education events from Janssen and Boehringer Ingelheim, has served as an advisor for Boehringer Ingelheim, and his research institute has received research grants on his behalf from Boehringer Ingelheim. The funder provided support in the form of salaries for author HM, but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of these authors are articulated in the ‘author contributions’ section.