Effect of administration and withdrawal of the sodium‐glucose cotransporter 2 inhibitor, tofogliflozin, on renal protection in individuals with type 2 diabetes mellitus and diabetic nephropathy: A multicenter, single‐arm study (RESTORE‐nephropathy study)
ABSTRACT Aims/Introduction The mechanisms of the renoprotective effects of sodium‐glucose cotransporter 2 inhibitors are unknown. This study aimed to explore the effect and mechanism of tofogliflozin on urinary albumin by administration, withdrawal, and re‐administration. Materials and Methods Indiv...
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2025-05-01
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| Series: | Journal of Diabetes Investigation |
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| Online Access: | https://doi.org/10.1111/jdi.70018 |
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| author | Ayako Shigeta Masami Tanaka Shu Meguro Jiro Morimoto Takatoshi Imai Akira Yamauchi Yasuhiko Kanazawa Toshihide Kawai Koichiro Azuma Satoru Yamada Sho Endo Hiroshi Itoh Kaori Hayashi |
| author_facet | Ayako Shigeta Masami Tanaka Shu Meguro Jiro Morimoto Takatoshi Imai Akira Yamauchi Yasuhiko Kanazawa Toshihide Kawai Koichiro Azuma Satoru Yamada Sho Endo Hiroshi Itoh Kaori Hayashi |
| author_sort | Ayako Shigeta |
| collection | DOAJ |
| description | ABSTRACT Aims/Introduction The mechanisms of the renoprotective effects of sodium‐glucose cotransporter 2 inhibitors are unknown. This study aimed to explore the effect and mechanism of tofogliflozin on urinary albumin by administration, withdrawal, and re‐administration. Materials and Methods Individuals with type 2 diabetes mellitus and stage 2 or 3 diabetic nephropathy were enrolled. Tofogliflozin was administered for 24 weeks, withdrawn for 12 weeks (withdrawal period), and re‐administered for 24 weeks. The primary endpoint was the change in urinary albumin/creatinine ratio (UACR). The secondary endpoints included hemoglobin A1c (HbA1c), hepatic biomarkers, lipid profiles, physical examinations, and blood counts. Results A total of 47 individuals were enrolled. UACR significantly decreased throughout the observation period. It also significantly decreased, increased, and again decreased during the period of the 1st administration, withdrawal, and re‐administration, respectively. HbA1c, body weight, waist circumference, and systolic blood pressure also showed the same tendency. Aspartate aminotransferase and alanine aminotransferase significantly decreased throughout the observation period, but did not increase during the withdrawal period. Conclusions Urinary albumin improved during the administration of tofogliflozin and worsened during its withdrawal, suggesting the reversibility of its renoprotective effect. The administration of tofogliflozin should be continued to avoid the reversal of glycemic control, renoprotective effects, and other beneficial effects. |
| format | Article |
| id | doaj-art-7e780585ac6b4e9590c4a4759c01de02 |
| institution | OA Journals |
| issn | 2040-1116 2040-1124 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Diabetes Investigation |
| spelling | doaj-art-7e780585ac6b4e9590c4a4759c01de022025-08-20T02:27:19ZengWileyJournal of Diabetes Investigation2040-11162040-11242025-05-0116581782610.1111/jdi.70018Effect of administration and withdrawal of the sodium‐glucose cotransporter 2 inhibitor, tofogliflozin, on renal protection in individuals with type 2 diabetes mellitus and diabetic nephropathy: A multicenter, single‐arm study (RESTORE‐nephropathy study)Ayako Shigeta0Masami Tanaka1Shu Meguro2Jiro Morimoto3Takatoshi Imai4Akira Yamauchi5Yasuhiko Kanazawa6Toshihide Kawai7Koichiro Azuma8Satoru Yamada9Sho Endo10Hiroshi Itoh11Kaori Hayashi12Department of Internal Medicine Keio University School of Medicine Tokyo JapanDepartment of Medicine, Adachi Medical Center Tokyo Women's Medical University School of Medicine Tokyo JapanDepartment of Internal Medicine Keio University School of Medicine Tokyo JapanDepartment of Endocrinology and Diabetes JCHO Saitama Medical Center Saitama JapanDepartment of Diabetes and Rheumatology Yokohama Municipal Citizen's Hospital Yokohama JapanSuruga Clinic Shizuoka JapanDepartment of Diabetes and Endocrinology Kawasaki Municipal Ida Hospital Kawasaki JapanDepartment of Internal Medicine Tokyo Saiseikai Central Hospital Tokyo JapanDepartment of Medicine, Nerima General Hospital and Public Interest Incorporated Foundation, Tokyo Healthcare Foundation Institute of Healthcare Quality Improvement Tokyo JapanDiabetes Center Kitasato University Kitasato Institute Hospital Tokyo JapanDepartment of Medicine Saitama City Hospital Saitama JapanCenter of Preventive Medicine Keio University Tokyo JapanDepartment of Internal Medicine Keio University School of Medicine Tokyo JapanABSTRACT Aims/Introduction The mechanisms of the renoprotective effects of sodium‐glucose cotransporter 2 inhibitors are unknown. This study aimed to explore the effect and mechanism of tofogliflozin on urinary albumin by administration, withdrawal, and re‐administration. Materials and Methods Individuals with type 2 diabetes mellitus and stage 2 or 3 diabetic nephropathy were enrolled. Tofogliflozin was administered for 24 weeks, withdrawn for 12 weeks (withdrawal period), and re‐administered for 24 weeks. The primary endpoint was the change in urinary albumin/creatinine ratio (UACR). The secondary endpoints included hemoglobin A1c (HbA1c), hepatic biomarkers, lipid profiles, physical examinations, and blood counts. Results A total of 47 individuals were enrolled. UACR significantly decreased throughout the observation period. It also significantly decreased, increased, and again decreased during the period of the 1st administration, withdrawal, and re‐administration, respectively. HbA1c, body weight, waist circumference, and systolic blood pressure also showed the same tendency. Aspartate aminotransferase and alanine aminotransferase significantly decreased throughout the observation period, but did not increase during the withdrawal period. Conclusions Urinary albumin improved during the administration of tofogliflozin and worsened during its withdrawal, suggesting the reversibility of its renoprotective effect. The administration of tofogliflozin should be continued to avoid the reversal of glycemic control, renoprotective effects, and other beneficial effects.https://doi.org/10.1111/jdi.70018Diabetic nephropathyDrug withdrawalRenal protectionTofogliflozinUrinary albumin |
| spellingShingle | Ayako Shigeta Masami Tanaka Shu Meguro Jiro Morimoto Takatoshi Imai Akira Yamauchi Yasuhiko Kanazawa Toshihide Kawai Koichiro Azuma Satoru Yamada Sho Endo Hiroshi Itoh Kaori Hayashi Effect of administration and withdrawal of the sodium‐glucose cotransporter 2 inhibitor, tofogliflozin, on renal protection in individuals with type 2 diabetes mellitus and diabetic nephropathy: A multicenter, single‐arm study (RESTORE‐nephropathy study) Journal of Diabetes Investigation Diabetic nephropathy Drug withdrawal Renal protection Tofogliflozin Urinary albumin |
| title | Effect of administration and withdrawal of the sodium‐glucose cotransporter 2 inhibitor, tofogliflozin, on renal protection in individuals with type 2 diabetes mellitus and diabetic nephropathy: A multicenter, single‐arm study (RESTORE‐nephropathy study) |
| title_full | Effect of administration and withdrawal of the sodium‐glucose cotransporter 2 inhibitor, tofogliflozin, on renal protection in individuals with type 2 diabetes mellitus and diabetic nephropathy: A multicenter, single‐arm study (RESTORE‐nephropathy study) |
| title_fullStr | Effect of administration and withdrawal of the sodium‐glucose cotransporter 2 inhibitor, tofogliflozin, on renal protection in individuals with type 2 diabetes mellitus and diabetic nephropathy: A multicenter, single‐arm study (RESTORE‐nephropathy study) |
| title_full_unstemmed | Effect of administration and withdrawal of the sodium‐glucose cotransporter 2 inhibitor, tofogliflozin, on renal protection in individuals with type 2 diabetes mellitus and diabetic nephropathy: A multicenter, single‐arm study (RESTORE‐nephropathy study) |
| title_short | Effect of administration and withdrawal of the sodium‐glucose cotransporter 2 inhibitor, tofogliflozin, on renal protection in individuals with type 2 diabetes mellitus and diabetic nephropathy: A multicenter, single‐arm study (RESTORE‐nephropathy study) |
| title_sort | effect of administration and withdrawal of the sodium glucose cotransporter 2 inhibitor tofogliflozin on renal protection in individuals with type 2 diabetes mellitus and diabetic nephropathy a multicenter single arm study restore nephropathy study |
| topic | Diabetic nephropathy Drug withdrawal Renal protection Tofogliflozin Urinary albumin |
| url | https://doi.org/10.1111/jdi.70018 |
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