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Biomedicines
Volume 13
Issue 6
10.3390/biomedicines13061287
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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)

by
Yuta Nakamura
1,
Ichiro Horie
1,*,
Hiroshi Yano
2,
Hiroshi Nomoto
3,4,
Tomoyasu Fukui
5,6,
Yoshihiko Yuyama
7,
Tomoyuki Kawamura
7,8,
Mariko Ueda
9,
Akane Yamamoto
9,
Yushi Hirota
9,
Yoshiki Kusunoki
10,
Kenro Nishida
11,
Dan Sekiguchi
12,
Yasutaka Maeda
12,
Masae Minami
12,
Ayako Nagayama
13,
Shimpei Iwata
14,
Hitomi Minagawa
15,
Shinya Furukawa
16,17,18,
Teruki Miyake
17,
Hiroaki Ueno
19,
Rei Chinen
20,
Yoshiro Nakayama
20,
Hiroaki Masuzaki
20,
Yasutaka Miyachi
21,
Yosuke Okada
22,
Mitsuhiro Okamoto
23,
Kaoru Ono
24,
Ken-ichi Tanaka
25,
Akira Kurozumi
25,
Takenori Sakai
26,
Hironori Yamasaki
27,
Jun-ichi Yasui
28,
Ayako Ito
29,
Atsushi Kawakami
1 and
Norio Abiru
1,30 on behalf of the IPRA-CKD Study Groupadd Show full author list remove Hide full author list
1
Department of Endocrinology and Metabolism, Nagasaki University Hospital, Nagasaki 852-8501, Japan
2
Clinical Research Center, Nagasaki University Hospital, Nagasaki 852-8501, Japan
3
Department of Rheumatology, Endocrinology and Nephrology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Hokkaido 060-8638, Japan
4
Division of Endocrinology, Metabolism, and Rheumatology, Department of Internal Medicine, Asahikawa Medical University, Asahikawa 078-8510, Japan
5
Division of Diabetes, Metabolism, and Endocrinology, Department of Medicine, Showa University School of Medicine, Shinagawa 142-8555, Japan
6
Seino Medical Clinic, Koriyama 963-8851, Japan
7
Division of Pediatrics, Osaka Metropolitan University Graduate School, Osaka 545-8585, Japan
8
Abeno Medical Clinic, Osaka 545-0052, Japan
9
Division of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan
10
Department of Diabetes, Endocrinology and Clinical Immunology, School of Medicine, Hyogo Medical University, Nishinomiya 663-8501, Japan
11
Division of Diabetes and Endocrinology, Kumamoto Central Hospital, Kumamoto 862-0965, Japan
12
Minami Diabetes Clinical Research Center, Clinic Masae Minami, Fukuoka 815-0071, Japan
13
Division of Endocrinology and Metabolism, Department of Internal Medicine, Kurume University School of Medicine, Kurume 830-0011, Japan
14
Division of Endocrinology and Metabolism, Yame General Hospital, Yame 834-0034, Japan
15
Division of Metabolism and Endocrinology, Faculty of Medicine, Saga University, Saga 849-8501, Japan
16
Health Services Center, Ehime University, Bunkyo, Matsuyama 790-8577, Japan
17
Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Toon 791-0295, Japan
18
Furukawa Clinic, Matsuyama 790-0943, Japan
19
Division of Hematology, Diabetes, and Endocrinology, Department of Internal Medicine, Faculty of Medicine, University of Miyazaki, Miyazaki 889-1692, Japan
20
Division of Endocrinology, Diabetes and Metabolism, Hematology, Rheumatology, Graduate School of Medicine, University of the Ryukyus, Nishihara 903-0215, Japan
21
Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan
22
First Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health, Kitakyushu 807-8555, Japan
23
Department of Endocrinology, Metabolism, Rheumatology and Nephrology, Faculty of Medicine, Oita University, Oita 879-5593, Japan
24
Department of Metabolic Medicine, Faculty of Life Sciences, Kumamoto University, Kumamoto 860-8556, Japan
25
Department of Rheumatology and Diabetes, Wakamatsu Hospital of the University of Occupational and Environmental Health, Kitakyushu 808-0024, Japan
26
Department of Internal Medicine, Yahatahama City General Hospital, Yahatahama 796-8502, Japan
27
Department of Diabetes and Endocrinology, Sasebo General Medical Center, Sasebo 857-8511, Japan
28
Department of Endocrinology and Metabolism, NHO Nagasaki Medical Center, Omura 856-0835, Japan
29
Center of Diabetes and Endocrinology, Sasebo Central Hospital, Sasebo 857-1165, Japan
30
Midori Clinic, Nagasaki 852-8034, Japan
 
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*
Author to whom correspondence should be addressed.
Biomedicines 2025, 13(6), 1287; https://doi.org/10.3390/biomedicines13061287
Submission received: 10 April 2025 / Revised: 14 May 2025 / Accepted: 21 May 2025 / Published: 23 May 2025
(This article belongs to the Section Molecular and Translational Medicine)
Versions Notes

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 < 60 mL/min/1.73 m2 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: ipragliflozin; type 1 diabetes; SGLT2 inhibitor; chronic kidney disease; renal outcome ipragliflozin; type 1 diabetes; SGLT2 inhibitor; chronic kidney disease; renal outcome

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MDPI and ACS Style

Nakamura, Y.; Horie, I.; Yano, H.; Nomoto, H.; Fukui, T.; Yuyama, Y.; Kawamura, T.; Ueda, M.; Yamamoto, A.; Hirota, Y.; et al. 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). Biomedicines 2025, 13, 1287. https://doi.org/10.3390/biomedicines13061287

AMA Style

Nakamura Y, Horie I, Yano H, Nomoto H, Fukui T, Yuyama Y, Kawamura T, Ueda M, Yamamoto A, Hirota Y, et al. 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). Biomedicines. 2025; 13(6):1287. https://doi.org/10.3390/biomedicines13061287

Chicago/Turabian Style

Nakamura, Yuta, Ichiro Horie, Hiroshi Yano, Hiroshi Nomoto, Tomoyasu Fukui, Yoshihiko Yuyama, Tomoyuki Kawamura, Mariko Ueda, Akane Yamamoto, Yushi Hirota, and et al. 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)" Biomedicines 13, no. 6: 1287. https://doi.org/10.3390/biomedicines13061287

APA Style

Nakamura, Y., Horie, I., Yano, H., Nomoto, H., Fukui, T., Yuyama, Y., Kawamura, T., Ueda, M., Yamamoto, A., Hirota, Y., Kusunoki, Y., Nishida, K., Sekiguchi, D., Maeda, Y., Minami, M., Nagayama, A., Iwata, S., Minagawa, H., Furukawa, S., ... Abiru, N., on behalf of the IPRA-CKD Study Group. (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). Biomedicines, 13(6), 1287. https://doi.org/10.3390/biomedicines13061287

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