Effects of SGLT2 Inhibition on Egfr and Glomerular and Tubular Damage Markers in Japanese Patients with Type 2 Diabetes

Background: Sodium-glucose cotransporter 2 (SGLT2) inhibitors are a new class of antihyperglycemic drugs that enhances insulin-independent urinary glucose excretion. Recent studies have suggested that SGLT2 inhibitors possess a renoprotective property in type 2 diabetes patients. However, evidence of the effects of SGLT2 inhibition on glomerular and tubular damage markers is lacking. The aim of this study was to examine the effect of SGLT2 inhibitors on renal function, especially on glomerular and tubular damage markers in patients with type 2 diabetes. Methods: We retrospectively analyzed data from 81 patients who used SGLT2 inhibitors. Next, we investigated whether treatment with SGLT2 inhibitors affected urinary damage markers including N-acetyl-beta-D-glucosaminidase (NAG), liver-type fatty acid-binding protein (L-FABP), type IV collagen, and beta2-microglobulin (beta2MG) in patients with type 2 diabetes. Results: In the retrospective study, SGLT2 inhibition reduced the estimated glomerular filtration rate (eGFR) at 4 and 12 weeks in a manner that was correlated with the baseline eGFR. In the longitudinal study, SGLT2 inhibition tended to increase the urinary damage marker levels with an accompanying decrease in eGFR after 1 month of use. The observed changes in eGFR and urinary damage markers were reversed at 3 months, even though both the HbA1c level and blood pressure were further improved. Conclusions: These results indicated that SGLT2 inhibition reduces the eGFR in a manner depending on the baseline eGFR levels and transiently increased the glomerular and tubular damage markers in patients with type 2 diabetes. J Endocrinol Metab. 2018;8(5):106-112 doi: https://doi.org/10.14740/jem531w