Program

SGLT2 inhibitor

[Speaker] Akira Nishiyama:1
[Co-author] Hirofumi Hitomi:1, Daisuke Nakano:1
1:Department of Pharmacology, Kagawa University Medical School, Japan

Recently, EMPA-REG OUTCOME study and CANVAS program have shown that treatment with SGLT2 inhibitors significantly improved renal outcome in patients with type 2 diabetes. Interestingly, these renoprotective effects of SGLT2 inhibitors are independent of their effects on blood sugar, body weight and blood pressure levels. It has been suggested that SGLT2 inhibitors will decrease glomerular pressure and improve glomerular hyperfiltration, because a rapid eGFR decline is often observed by treatment with SGLT2 inhibitors during the first weeks of treatment. It is also speculated that SGLT2 inhibitor-induced reduction in glomerular pressure is associated with an activation of tubuloglomerular feedback mechanism by an increase in solute delivery at the macula densa. Indeed, many clinical studies have also shown that treatment with SGLT2 inhibitors significantly decrease albuminuria independent of reductions in blood sugar, body weight and blood pressure levels. However, during treatment with SGLT2 inhibitor, there is no relationship between reductions in albuminuria and eGFR. In addition, recent animal studies have shown that SGLT2 inhibitors do not improve albuminuria in 5/6 nephrectomized glomerular hypertensive rats, indicating that renoprotective effects of SGLT2 cannot solely be explained by reduction in glomerular pressure. In this regard, we have recently shown that SGLT2 inhibition protects proximal tubular cells and peritubular capillaries. These data suggest that SGLT2 inhibitors elicit their renoprotective effects through multiple mechanisms.
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