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Publication
Differential Effects of Empagliflozin on Microvascular Complications in Murine
Models of Type 1 and Type 2 Diabetes.
Authors Eid SA, O'Brien PD, Hinder LM, Hayes JM, Mendelson FE, Zhang H, Zeng L, Kretzler
K, Narayanan S, Abcouwer SF, Brosius Iii FC, Pennathur S, Savelieff MG, Feldman
EL
Submitted By Submitted Externally on 11/10/2020
Status Published
Journal Biology
Year 2020
Date Published 10/1/2020
Volume : Pages 9 : Not Specified
PubMed Reference 33105667
Abstract Microvascular complications account for the significant morbidity associated
with diabetes. Despite tight glycemic control, disease risk remains especially
in type 2 diabetes (T2D) patients and no therapy fully prevents nerve, retinal,
or renal damage in type 1 diabetes (T1D) or T2D. Therefore, new antidiabetic
drug classes are being evaluated for the treatment of microvascular
complications. We investigated the effect of empagliflozin (EMPA), an inhibitor
of the sodium/glucose cotransporter 2 (SGLT2), on diabetic neuropathy (DPN),
retinopathy (DR), and kidney disease (DKD) in streptozotocin-induced T1D and
db/db T2D mouse models. EMPA lowered blood glycemia in T1D and T2D models.
However, it did not ameliorate any microvascular complications in the T2D model,
which was unexpected, given the protective effect of SGLT2 inhibitors on DKD
progression in T2D subjects. Although EMPA did not improve DKD in the T1D model,
it had a potential modest effect on DR measures and favorably impacted DPN as
well as systemic oxidative stress. These results support the concept that
glucose-centric treatments are more effective for DPN in T1D versus T2D. This is
the first study that provides an evaluation of EMPA treatment on all
microvascular complications in a side-by-side comparison in T1D and T2D models.




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