Different renoprotective effects of luseogliflozin depend on the renal function at the baseline in patients with type 2 diabetes: A retrospective study during 12 months before and after initiation.

AimsThe safety and efficacy, particularly, the factors associated with the renal prognosis, were assessed over 12 months after the initiation of luseogliflozin therapy in Japanese patients with type 2 diabetes and renal impairment.MethodsIn total, 238 patients treated with luseogliflozin (2.5 mg, once daily) were studied as the safety analysis set. Two hundred and two subjects whose medication was continued over 12 months were investigated as the full analysis set. The subjects were divided into 3 groups based on the estimated glomerular filtration rate (eGFR): high eGFR (n = 49), normal eGFR (n = 116) and low eGFR (n = 37) groups.ResultsThe body weight, systolic blood pressure, HbA1c and urinary protein excretion gradually decreased from baseline in all eGFR groups. While the eGFR was significantly reduced from baseline in the high and normal eGFR groups, the eGFR did not significantly differ over time in the low eGFR group. There was no marked difference in the frequency of adverse events that were specific for SGLT2 inhibitors among the 3 groups in the safety analysis set.ConclusionsLuseogliflozin can preserve the renal function in the medium term in patients with type 2 diabetes and renal impairment without an increase in specific adverse events

The clinical characteristics of the full analysis set at baseline.

The clinical characteristics of the full analysis set at baseline.</p

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- (2, n = 43) eGFR groups. GLP-1, glucagon-like peptide-1; eGFR, estimated glomerular filtration rate; SGLT2, Sodium-glucose cotransporter 2.</p

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.</p

Changes in the eGFR in 102 patients treated over 12 months before the initiation of tofogliflozin administration.

Changes in the eGFR in 102 patients treated over 12 months before the initiation of tofogliflozin administration.</p

Adverse events during the observation period in the safety analysis set.

Adverse events during the observation period in the safety analysis set.</p

Dataset for data analyses.

BackgroundThe 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.MethodsIn 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 2, n = 43) eGFR groups.ResultsThe 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.ConclusionsTofogliflozin may preserve renal function in the medium term in patients with type 2 diabetes and kidney impairment without an increase in specific adverse events.</div

Relationship between the changes in the eGFR and the clinical parameters at baseline in the full analysis set.

Relationship between the changes in the eGFR and the clinical parameters at baseline in the full analysis set.</p

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- (2, 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.</p