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Kidney Outcomes Associated With SGLT2 Inhibitors Versus Other Glucose-Lowering Drugs in Real-world Clinical Practice: The Japan Chronic Kidney Disease Database

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posted on 2021-09-29, 13:14 authored by Hajime Nagasu, Yuichiro Yano, Hiroshi Kanegae, Hiddo J.L. Heerspink, Masaomi Nangaku, Yosuke Hirakawa, Yuka Sugawara, Naoki Nakagawa, Yuji Tani, Jun Wada, Hitoshi Sugiyama, Kazuhiko Tsuruya, Toshiaki Nakano, Shoichi Maruyama, Takashi Wada, Kunihiro Yamagata, Ichiei Narita, Kouichi Tamura, Motoko Yanagita, Yoshio Terada, Takashi Shigematsu, Tadashi Sofue, Takafumi Ito, Hirokazu Okada, Naoki Nakashima, Hiromi Kataoka, Kazuhiko Ohe, Mihoko Okada, Seiji Itano, Akira Nishiyama, Eiichiro Kanda, Kohjiro Ueki, Naoki Kashihara
Objective: Randomized controlled trials have shown kidney protective effects of sodium glucose transporter 2 (SGLT2) inhibitors, and clinical practice databases have suggested that these effects translate to clinical practice. However, long-term efficacy as well as whether the presence or absence of proteinuria and the rate of estimated glomerular filtration rates (eGFR) decline prior to SGLT2 inhibitors initiation modifies treatment efficacy among type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD) patients is unknown.

Research Design and Methods: Using the Japan Chronic Kidney Disease Database (J-CKD-DB), a nationwide multicenter CKD registry, we developed propensity scores for SGLT2 inhibitor initiation, with 1:1 matching with patients who were initiated on other glucose-lowering drugs. The primary outcome included rate of eGFR decline, and the secondary outcomes included a composite outcome of 50% eGFR decline or end-stage kidney disease.

Results: At baseline, mean age at initiation of the SGLT2 inhibitor (n=1,033) or other glucose-lowering drug (n=1,033) was 64.4 years; mean eGFR was 68.1 mL/min per 1.73 m²; and proteinuria was apparent in 578 (28.0%) of included patients. During follow-up, SGLT2 inhibitor initiation was associated with reduced eGFR decline (difference in slope for SGLT2 inhibitors vs other drugs 0.75 mL/min/1.73 m² per year (0.51 to 1.00). During a mean follow-up of 24 months, 103 composite kidney outcomes occurred: 30 (14 events per 1,000 patient-years) among the SGLT2 inhibitors group and 73 (36 events per 1,000 patient-years) among the other drugs group (hazard ratio 0.40, 95% CI 0.26 to 0.61). The benefit provided by SGLT2 inhibitors was consistent irrespective of proteinuria and rate of eGFR decline before initiating SGLT2 inhibitors (pheterogeneity ≥0.35).

Conclusions: The benefits of SGLT2 inhibitors on kidney function as observed in clinical trials translate to patients treated in clinical practice with no evidence that the effects are modified by the underlying rate of kidney function decline or the presence of proteinuria.


This work was supported in part by grants for Development of Comprehensive Database of Chronic Kidney Disease, Research on Policy Planning and Evaluation from the Ministry of Health, Labour and Welfare of Japan awarded to NK (19AC1002), and Japan Agency for Medical Research and Development, Practical Research Project for Life-Style related Diseases including Cardiovascular Diseases and Diabetes Mellitus and Platform Program for Promotion of Genome Medicine in the form of grants awarded to Dr. Kashihara (20ek0210135h0001, 19ek0210095h0003, 20km0405210h0003).


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