Adjunct Therapy with Ipragliflozin Exerts Limited Effects on Kidney Protection in Type 1 Diabetes: A Retrospective Study Conducted at 25 Centers in Japan (IPRA-CKD)

<b>Background/Objectives</b>: While sodium-glucose cotransporter 2 (SGLT2) inhibitors have demonstrated additional non-glycemic benefits for renal protection in individuals with type 2 diabetes, less evidence is available for those with type 1 diabetes (T1D). To determine whether the adjunctive use of the SGLT2 inhibitor ipragliflozin confers kidney protection in individuals with T1D, we retrospectively analyzed data from a real-world cohort examined at 25 centers in Japan. <b>Methods</b>: We enrolled 359 subjects aged 20-74 years with T1D (IPRA group: 159 ipragliflozin users; control [CTRL] group: 200 non-users). The primary outcome was changes in the estimated glomerular filtration rate (eGFR) from baseline to 24 months after the initiation of ipragliflozin. The secondary outcomes were all other changes, including the urinary albumin-creatinine ratio (UACR) and urinary protein-creatinine ratio (UPCR). <b>Results</b>: The IPRA group's eGFR decline slopes were 0.79 mL/min/1.73 m<sup>2</sup>/year milder than the CTRL group's after propensity score matching, but this difference was not significant. The subjects complicated by chronic kidney disease (CKD) defined as UACR ≥ 30 mg/g and/or UPCR ≥ 0.5 g/g and/or eGFR < 60 mL/min/1.73 m<sup>2</sup> showed changes in UPCR (g/g) from baseline to 24 months that were significantly lower in the IPRA group (-0.27 ± 1.63) versus the CTRL group (0.18 ± 0.36) (<i>p</i> = 0.016). No significant increase in adverse events (including severe hypoglycemia and hospitalization due to ketosis/ketoacidosis or cardiovascular diseases) was observed in the IPRA group. <b>Conclusions</b>: Adjunctive treatment with ipragliflozin exerted potential renal benefits by decreasing proteinuria in T1D subjects with CKD. Further investigations are required to determine whether its additional benefits exceed the increased risk of ketoacidosis.

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Publication Details

Journal
Biomedicines
Published
2025-05-23
DOI
https://doi.org/10.3390/biomedicines13061287
Primary Topic
Diabetes Treatment and Management
Type
article
Field-Weighted Citation Impact
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article

Adjunct Therapy with Ipragliflozin Exerts Limited Effects on Kidney Protection in Type 1 Diabetes: A Retrospective Study Conducted at 25 Centers in Japan (IPRA-CKD)

Yosuke Okada, Akira Kurozumi, Yasutaka Miyachi, Tomoyuki Kawamura et al.
Biomedicines
Diabetes Treatment and Management
article

Adjunct Therapy with Ipragliflozin Exerts Limited Effects on Kidney Protection in Type 1 Diabetes: A Retrospective Study Conducted at 25 Centers in Japan (IPRA-CKD)

Yosuke Okada, Akira Kurozumi, Yasutaka Miyachi, Tomoyuki Kawamura, Mitsuhiro Okamoto, Yushi Hirota, Hideki Minagawa, Yoshiki Kusunoki, Teruki Miyake, Hiroaki Masuzaki, Hiroaki Ueno, Tomoyasu Fukui, Dan Sekiguchi, Yasutaka Maeda, Hironori Yamasaki, Hiroshi Nomoto, Shinya Furukawa, Ichiro Horie, Ayako Nagayama, Kenro Nishida, Yuta Nakamura, Yoshihiko Yuyama, Norio Abiru, Junichi Yasui, Akane Yamamoto, Kenichi Tanaka, Atsushi Kawakami, Ayako Ito, Kaoru Ono, Shimpei Iwata, Masae Minami, Yoshiro Nakayama, Takenori Sakai, Yano Hiroshi, Mariko Ueda, Rei Chinen
article en

Abstract

<b>Background/Objectives</b>: While sodium-glucose cotransporter 2 (SGLT2) inhibitors have demonstrated additional non-glycemic benefits for renal protection in individuals with type 2 diabetes, less evidence is available for those with type 1 diabetes (T1D). To determine whether the adjunctive use of the SGLT2 inhibitor ipragliflozin confers kidney protection in individuals with T1D, we retrospectively analyzed data from a real-world cohort examined at 25 centers in Japan. <b>Methods</b>: We enrolled 359 subjects aged 20-74 years with T1D (IPRA group: 159 ipragliflozin users; control [CTRL] group: 200 non-users). The primary outcome was changes in the estimated glomerular filtration rate (eGFR) from baseline to 24 months after the initiation of ipragliflozin. The secondary outcomes were all other changes, including the urinary albumin-creatinine ratio (UACR) and urinary protein-creatinine ratio (UPCR). <b>Results</b>: The IPRA group's eGFR decline slopes were 0.79 mL/min/1.73 m<sup>2</sup>/year milder than the CTRL group's after propensity score matching, but this difference was not significant. The subjects complicated by chronic kidney disease (CKD) defined as UACR ≥ 30 mg/g and/or UPCR ≥ 0.5 g/g and/or eGFR < 60 mL/min/1.73 m<sup>2</sup> showed changes in UPCR (g/g) from baseline to 24 months that were significantly lower in the IPRA group (-0.27 ± 1.63) versus the CTRL group (0.18 ± 0.36) (<i>p</i> = 0.016). No significant increase in adverse events (including severe hypoglycemia and hospitalization due to ketosis/ketoacidosis or cardiovascular diseases) was observed in the IPRA group. <b>Conclusions</b>: Adjunctive treatment with ipragliflozin exerted potential renal benefits by decreasing proteinuria in T1D subjects with CKD. Further investigations are required to determine whether its additional benefits exceed the increased risk of ketoacidosis.

BiomedicinesVol. 13(6)
Kurume University (JP), University of Miyazaki (JP), SHOWA Medical University (JP), Kyushu University (JP), Asahikawa Medical University (JP), Saga University (JP), University of Occupational and Environmental Health Japan (JP), Oita University (JP), Hokkaido University (JP), University of the Ryukyus (JP), Sasebo City General Hospital (JP), Hiroshima Kyoritsu Hospital (JP), SOUSEIKAI Global Clinical Research Center (JP), Nagasaki Medical Center (JP), Furukawa Electric (Japan) (JP), Kumamoto Chuo Hospital (JP), Saiseikai Yahata General Hospital (JP), Nagasaki University Hospital (JP), Ehime University (JP), Osaka Metropolitan University (JP), Kobe University (JP), Tokyo Metropolitan University (JP), Kumamoto University (JP)
Astellas Pharma, Hokkaido University, Astellas Foundation for Research on Metabolic Disorders
Openalex Percentile: Top 84%
Diabetes Treatment and Management
DOIOpen Access PDFOpenAlex
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