Effects of canagliflozin on kidney oxygenation evaluated using blood oxygenation level-dependent MRI in patients with type 2 diabetes.

Background: Recent clinical studies suggest protective effects of SGLT2 inhibitors on kidney disease outcome. Chronic hypoxia has a critical role in kidney disease development, thus we speculated that canagliflozin, an SGLT2 inhibitor, can improve kidney oxygenation.
Methods: A single-arm study was conducted to investigate the effects of canagliflozin on T2* value, which reflects oxygenation level, in patients with type 2 diabetes (T2D) using repeated blood oxygenation level-dependent MRI (BOLD MRI) examinations. Changes in cortical T2* from before (Day 0) to after single-dose treatment (Day 1) and after five consecutive treatments (Day 5) were evaluated using 12-layer concentric objects (TLCO) and region of interest (ROI) methods.
Results: In the full analysis set (n=14 patients), the TLCO method showed no change of T2* with canagliflozin treatment, whereas the ROI method found that cortical T2* was significantly increased on Day 1 but not on Day 5. Sensitivity analysis using TLCO in 13 well-measured patients showed that canagliflozin significantly increased T2* on Day 1 with no change on Day 5, whereas a significant improvement in cortical T2* following canagliflozin treatment was found on both Day 1 and 5 using ROI.
Conclusions: Short-term canagliflozin treatment may improve cortical oxygenation and lead to better kidney outcomes in patients with T2D.
Competing Interests: KM has received speaker fees from Mitsubishi Tanabe Pharma Corporation, Daiichi Sankyo Co., Nippon Boehringer Ingelheim Co., Eli Lilly Japan K.K., AstraZeneca K.K., Ono Pharmaceutical Co. Ltd., Novo Nordisk Pharma Ltd., Kyowa Kirin Co. Ltd., and Mochida Pharmaceutical Co. Ltd., and unrestricted research grants from Chugai Pharmaceutical Co. Ltd, Kyowa Kirin Co. Ltd., Torii Pharmaceutical Co. Ltd., and Sumitomo Pharma Co. Ltd., and research funding from Kyowa Kirin Co. Ltd. TI has received speaker fees from Mitsubishi Tanabe Pharma Corporation, Daiichi Sankyo Co., Nippon Boehringer Ingelheim Co., Eli Lilly Japan K.K., AstraZeneca K.K., Ono Pharmaceutical Co. Ltd., Novo Nordisk Pharma Ltd., Kyowa Kirin Co. Ltd., Mochida Pharmaceutical Co. Ltd., Torii Pharmaceutical Co. Ltd., Otsuka Pharmaceutical Co., Ltd., Sanwa Kagaku Kenkyusho CO., LTD., and Bayer Yakuhin, Ltd., and unrestricted research grant from Eli Lilly Japan K.K. HU has received speaker fees from Mitsubishi Tanabe Pharma Corporation, Daiichi Sankyo Co., Kyowa Kirin, and Mochida Pharmaceutical Co., Ltd. SN has received speaker fees from AstraZeneca K.K., Ono Pharmaceutical Co. Ltd., Otsuka Pharmaceutical Co., Ltd., Novartis Pharmaceutical Co. Ltd., and Chugai Pharmaceutical Co. Ltd. ST has received speaker fees from Chugai Pharmaceutical Co., Ltd., Daiichi Sankyo Co., Ltd., Kyowa Kirin Co., Ltd., and Takeda Pharmaceutical Co., Ltd. HO has received speaker fees from Mitsubishi Tanabe Pharma Corporation, Daiichi Sankyo Co., Nippon Boehringer Ingelheim Co., Eli Lilly Japan K.K., AstraZeneca K.K., Ono Pharmaceutical Co. Ltd., Kyowa Kirin Co. Ltd., Novartis Pharmaceutical Co. Ltd., Torii Pharmaceutical Co. Ltd., Otsuka Pharmaceutical Co. Ltd., and Bayer Pharmaceutical Co. Ltd., and unrestricted research grants from Ono Pharmaceutical Co. Ltd., Kyowa Kirin Co. Ltd., Torii Pharmaceutical Co. Ltd., Chugai Pharmaceutical Co. Ltd., and Bayer Pharmaceutical Co. Ltd., and research funding from Kyowa Kirin Co. Ltd., Torii Pharmaceutical Co. Ltd., Kissei Pharmaceutical Co. Ltd., Chugai Pharmaceutical Co. Ltd., and Bayer Pharmaceutical Co. Ltd. ME has received speaker fees from Novo Nordisk Pharma Ltd., Nippon Boehringer Ingelheim Co., Sumitomo Pharma Co. Ltd., Sanofi K.K., Kyowa Kirin Co. Ltd., AstraZeneca K.K., and Ono Pharmaceutical Co. Ltd., and unrestricted research grants from Sumitomo Pharma Co. Ltd., Nippon Boehringer Ingelheim Co., Eisai Co. Ltd., Kyowa Kirin Co. Ltd., Mitsubishi Tanabe Pharma Corporation, Chugai Pharmaceutical Co. Ltd, and Bayer Pharmaceutical Co. Ltd. and research funding from Mitsubishi Tanabe Pharma Corporation and Kyowa Kirin Co. Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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