Changes in the estimated glomerular filtration rate and predictors of the renal prognosis in Japanese patients with type 2 diabetes: A retrospective study during the 12 months after the initiation of tofogliflozin

Abstract

Background: The changes in the estimated glomerular filtration rate (eGFR) and predictors of the renal prognosis were retrospectively assessed over the 12 months after the initiation of tofogliflozin, which has the shortest half-life among sodium-glucose cotransporter 2 (SGLT2) inhibitors, in Japanese patients with type 2 diabetes and renal impairment.

Methods: In total, 158 patients treated with tofogliflozin between 2019 and 2021 were studied as the safety analysis set. One hundred and thirty subjects whose medication was continued over 12 months were investigated as the full analysis set. The subjects were divided into two groups based on the eGFR: normal- (eGFR ≥60 mL/min/1.73 m2, n = 87) and low- (eGFR <60 mL/min/1.73 m2, n = 43) eGFR groups.

Results: The body weight, blood pressure, urinary protein excretion, and serum uric acid concentration decreased from baseline in both eGFR groups while the hemoglobin level increased. The eGFR did not significantly differ over time, except for the initial dip (-4.3±9.6 mL/min/1.73 m2 in the normal-eGFR group and -1.5±5.3 mL/min/1.73 m2 in the low-eGFR group). The change in the eGFR at 12 months after the initiation of tofogliflozin was -1.9±9.0 mL/min/1.73 m2 and 0.2±6.0 mL/min/1.73 m2 in the normal- and low-eGFR group, respectively. In the normal-eGFR group, the change in the eGFR showed a significant negative correlation with the HbA1c and eGFR at baseline, according to a multiple regression analysis. In the low-eGFR group, the change in the eGFR showed a significant negative correlation with urate-lowering agent use. The frequencies of adverse events specific for SGLT2 inhibitors were not significantly different between the normal- and low-eGFR groups.

Conclusions: Tofogliflozin may preserve renal function in the medium term in patients with type 2 diabetes and kidney impairment without an increase in specific adverse events.

Fig 1. Flowchart of patient selection.

The safety of tofogliflozin was analyzed in the safety analysis set (n = 158), and the effectiveness was investigated in the full analysis set (n = 130). The analysis sets were divided into the normal- (≥60 mL/min/1.73 m², n = 87) and low- (<60 mL/min/1.73 m², n = 43) eGFR groups. GLP-1, glucagon-like peptide-1; eGFR, estimated glomerular filtration rate; SGLT2, Sodium-glucose cotransporter 2.

Fig 2. Changes in the eGFR in the groups according to the eGFR at baseline (0 months) before and after the initiation of tofogliflozin (n = 102).

(A) The closed (black) circles and open (white) squares indicate subjects in the normal- (≥60 mL/min/1.73 m², n = 68) and low- (<60 mL/min/1.73 m², n = 34) eGFR groups, respectively. *P <0.05 and **P <0.01 vs. baseline (0 months) value. (B) Closed (black) and open (white) bars indicate the differences in the eGFR in the normal- and low-eGFR group, respectively. #P <0.05 vs. corresponding value before the initiation of tofogliflozin. eGFR, estimated glomerular filtration rate.

Fig 3

Relationships between the change in the eGFR after the initiation of tofogliflozin and (A) HbA1c at the baseline, (B) eGFR at the baseline, (C) change in HbA1c after the initiation of tofogliflozin and (D) change in serum uric acid concentration after the initiation of tofogliflozin. GFR, estimated glomerular filtration rate.