Biomedicines (May 2025)
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)
- Yuta Nakamura,
- Ichiro Horie,
- Hiroshi Yano,
- Hiroshi Nomoto,
- Tomoyasu Fukui,
- Yoshihiko Yuyama,
- Tomoyuki Kawamura,
- Mariko Ueda,
- Akane Yamamoto,
- Yushi Hirota,
- Yoshiki Kusunoki,
- Kenro Nishida,
- Dan Sekiguchi,
- Yasutaka Maeda,
- Masae Minami,
- Ayako Nagayama,
- Shimpei Iwata,
- Hitomi Minagawa,
- Shinya Furukawa,
- Teruki Miyake,
- Hiroaki Ueno,
- Rei Chinen,
- Yoshiro Nakayama,
- Hiroaki Masuzaki,
- Yasutaka Miyachi,
- Yosuke Okada,
- Mitsuhiro Okamoto,
- Kaoru Ono,
- Ken-ichi Tanaka,
- Akira Kurozumi,
- Takenori Sakai,
- Hironori Yamasaki,
- Jun-ichi Yasui,
- Ayako Ito,
- Atsushi Kawakami,
- Norio Abiru
Affiliations
- Yuta Nakamura
- Department of Endocrinology and Metabolism, Nagasaki University Hospital, Nagasaki 852-8501, Japan
- Ichiro Horie
- Department of Endocrinology and Metabolism, Nagasaki University Hospital, Nagasaki 852-8501, Japan
- Hiroshi Yano
- Clinical Research Center, Nagasaki University Hospital, Nagasaki 852-8501, Japan
- Hiroshi Nomoto
- Department of Rheumatology, Endocrinology and Nephrology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo 060-8638, Japan
- Tomoyasu Fukui
- Division of Diabetes, Metabolism, and Endocrinology, Department of Medicine, Showa University School of Medicine, Shinagawa 142-8555, Japan
- Yoshihiko Yuyama
- Division of Pediatrics, Osaka Metropolitan University Graduate School, Osaka 545-8585, Japan
- Tomoyuki Kawamura
- Division of Pediatrics, Osaka Metropolitan University Graduate School, Osaka 545-8585, Japan
- Mariko Ueda
- Division of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan
- Akane Yamamoto
- Division of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan
- Yushi Hirota
- Division of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan
- Yoshiki Kusunoki
- Department of Diabetes, Endocrinology and Clinical Immunology, School of Medicine, Hyogo Medical University, Nishinomiya 663-8501, Japan
- Kenro Nishida
- Division of Diabetes and Endocrinology, Kumamoto Central Hospital, Kumamoto 862-0965, Japan
- Dan Sekiguchi
- Minami Diabetes Clinical Research Center, Clinic Masae Minami, Fukuoka 815-0071, Japan
- Yasutaka Maeda
- Minami Diabetes Clinical Research Center, Clinic Masae Minami, Fukuoka 815-0071, Japan
- Masae Minami
- Minami Diabetes Clinical Research Center, Clinic Masae Minami, Fukuoka 815-0071, Japan
- Ayako Nagayama
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Kurume University School of Medicine, Kurume 830-0011, Japan
- Shimpei Iwata
- Division of Endocrinology and Metabolism, Yame General Hospital, Yame 834-0034, Japan
- Hitomi Minagawa
- Division of Metabolism and Endocrinology, Faculty of Medicine, Saga University, Saga 849-8501, Japan
- Shinya Furukawa
- Health Services Center, Ehime University, Bunkyo, Matsuyama 790-8577, Japan
- Teruki Miyake
- Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Toon 791-0295, Japan
- Hiroaki Ueno
- Division of Hematology, Diabetes, and Endocrinology, Department of Internal Medicine, Faculty of Medicine, University of Miyazaki, Miyazaki 889-1692, Japan
- Rei Chinen
- Division of Endocrinology, Diabetes and Metabolism, Hematology, Rheumatology, Graduate School of Medicine, University of the Ryukyus, Nishihara 903-0215, Japan
- Yoshiro Nakayama
- Division of Endocrinology, Diabetes and Metabolism, Hematology, Rheumatology, Graduate School of Medicine, University of the Ryukyus, Nishihara 903-0215, Japan
- Hiroaki Masuzaki
- Division of Endocrinology, Diabetes and Metabolism, Hematology, Rheumatology, Graduate School of Medicine, University of the Ryukyus, Nishihara 903-0215, Japan
- Yasutaka Miyachi
- Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan
- Yosuke Okada
- First Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health, Kitakyushu 807-8555, Japan
- Mitsuhiro Okamoto
- Department of Endocrinology, Metabolism, Rheumatology and Nephrology, Faculty of Medicine, Oita University, Oita 879-5593, Japan
- Kaoru Ono
- Department of Metabolic Medicine, Faculty of Life Sciences, Kumamoto University, Kumamoto 860-8556, Japan
- Ken-ichi Tanaka
- Department of Rheumatology and Diabetes, Wakamatsu Hospital of the University of Occupational and Environmental Health, Kitakyushu 808-0024, Japan
- Akira Kurozumi
- Department of Rheumatology and Diabetes, Wakamatsu Hospital of the University of Occupational and Environmental Health, Kitakyushu 808-0024, Japan
- Takenori Sakai
- Department of Internal Medicine, Yahatahama City General Hospital, Yahatahama 796-8502, Japan
- Hironori Yamasaki
- Department of Diabetes and Endocrinology, Sasebo General Medical Center, Sasebo 857-8511, Japan
- Jun-ichi Yasui
- Department of Endocrinology and Metabolism, NHO Nagasaki Medical Center, Omura 856-0835, Japan
- Ayako Ito
- Center of Diabetes and Endocrinology, Sasebo Central Hospital, Sasebo 857-1165, Japan
- Atsushi Kawakami
- Department of Endocrinology and Metabolism, Nagasaki University Hospital, Nagasaki 852-8501, Japan
- Norio Abiru
- Department of Endocrinology and Metabolism, Nagasaki University Hospital, Nagasaki 852-8501, Japan
- DOI
- https://doi.org/10.3390/biomedicines13061287
- Journal volume & issue
-
Vol. 13,
no. 6
p. 1287
Abstract
Background/Objectives: 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. Methods: 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). Results: The IPRA group’s eGFR decline slopes were 0.79 mL/min/1.73 m2/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 2 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) (p = 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. Conclusions: 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.
Keywords
