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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

OBJECTIVE: Randomized controlled trials have shown kidney-protective effects of sodium–glucose cotransporter 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...

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Autores principales: Nagasu, Hajime, Yano, Yuichiro, Kanegae, Hiroshi, Heerspink, Hiddo J.L., Nangaku, Masaomi, Hirakawa, Yosuke, Sugawara, Yuka, Nakagawa, Naoki, Tani, Yuji, Wada, Jun, Sugiyama, Hitoshi, Tsuruya, Kazuhiko, Nakano, Toshiaki, Maruyama, Shoichi, Wada, Takashi, Yamagata, Kunihiro, Narita, Ichiei, Tamura, Kouichi, Yanagita, Motoko, Terada, Yoshio, Shigematsu, Takashi, Sofue, Tadashi, Ito, Takafumi, Okada, Hirokazu, Nakashima, Naoki, Kataoka, Hiromi, Ohe, Kazuhiko, Okada, Mihoko, Itano, Seiji, Nishiyama, Akira, Kanda, Eiichiro, Ueki, Kohjiro, Kashihara, Naoki
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Diabetes Association 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8546274/
https://www.ncbi.nlm.nih.gov/pubmed/34593566
http://dx.doi.org/10.2337/dc21-1081
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author Nagasu, Hajime
Yano, Yuichiro
Kanegae, Hiroshi
Heerspink, Hiddo J.L.
Nangaku, Masaomi
Hirakawa, Yosuke
Sugawara, Yuka
Nakagawa, Naoki
Tani, Yuji
Wada, Jun
Sugiyama, Hitoshi
Tsuruya, Kazuhiko
Nakano, Toshiaki
Maruyama, Shoichi
Wada, Takashi
Yamagata, Kunihiro
Narita, Ichiei
Tamura, Kouichi
Yanagita, Motoko
Terada, Yoshio
Shigematsu, Takashi
Sofue, Tadashi
Ito, Takafumi
Okada, Hirokazu
Nakashima, Naoki
Kataoka, Hiromi
Ohe, Kazuhiko
Okada, Mihoko
Itano, Seiji
Nishiyama, Akira
Kanda, Eiichiro
Ueki, Kohjiro
Kashihara, Naoki
author_facet Nagasu, Hajime
Yano, Yuichiro
Kanegae, Hiroshi
Heerspink, Hiddo J.L.
Nangaku, Masaomi
Hirakawa, Yosuke
Sugawara, Yuka
Nakagawa, Naoki
Tani, Yuji
Wada, Jun
Sugiyama, Hitoshi
Tsuruya, Kazuhiko
Nakano, Toshiaki
Maruyama, Shoichi
Wada, Takashi
Yamagata, Kunihiro
Narita, Ichiei
Tamura, Kouichi
Yanagita, Motoko
Terada, Yoshio
Shigematsu, Takashi
Sofue, Tadashi
Ito, Takafumi
Okada, Hirokazu
Nakashima, Naoki
Kataoka, Hiromi
Ohe, Kazuhiko
Okada, Mihoko
Itano, Seiji
Nishiyama, Akira
Kanda, Eiichiro
Ueki, Kohjiro
Kashihara, Naoki
author_sort Nagasu, Hajime
collection PubMed
description OBJECTIVE: Randomized controlled trials have shown kidney-protective effects of sodium–glucose cotransporter 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 inhibitor initiation modify 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 m(2), 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 m(2) 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 0.26–0.61). The benefit provided by SGLT2 inhibitors was consistent irrespective of proteinuria and rate of eGFR decline before initiation of SGLT2 inhibitors (P(heterogeneity) ≥ 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.
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spelling pubmed-85462742021-11-02 Kidney Outcomes Associated With SGLT2 Inhibitors Versus Other Glucose-Lowering Drugs in Real-world Clinical Practice: The Japan Chronic Kidney Disease Database Nagasu, Hajime Yano, Yuichiro Kanegae, Hiroshi Heerspink, Hiddo J.L. Nangaku, Masaomi Hirakawa, Yosuke Sugawara, Yuka Nakagawa, Naoki Tani, Yuji Wada, Jun Sugiyama, Hitoshi Tsuruya, Kazuhiko Nakano, Toshiaki Maruyama, Shoichi Wada, Takashi Yamagata, Kunihiro Narita, Ichiei Tamura, Kouichi Yanagita, Motoko Terada, Yoshio Shigematsu, Takashi Sofue, Tadashi Ito, Takafumi Okada, Hirokazu Nakashima, Naoki Kataoka, Hiromi Ohe, Kazuhiko Okada, Mihoko Itano, Seiji Nishiyama, Akira Kanda, Eiichiro Ueki, Kohjiro Kashihara, Naoki Diabetes Care Emerging Therapies: Drugs and Regimens OBJECTIVE: Randomized controlled trials have shown kidney-protective effects of sodium–glucose cotransporter 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 inhibitor initiation modify 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 m(2), 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 m(2) 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 0.26–0.61). The benefit provided by SGLT2 inhibitors was consistent irrespective of proteinuria and rate of eGFR decline before initiation of SGLT2 inhibitors (P(heterogeneity) ≥ 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. American Diabetes Association 2021-11 2021-10-18 /pmc/articles/PMC8546274/ /pubmed/34593566 http://dx.doi.org/10.2337/dc21-1081 Text en © 2021 by the American Diabetes Association https://www.diabetesjournals.org/content/licenseReaders may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. More information is available at https://www.diabetesjournals.org/content/license.
spellingShingle Emerging Therapies: Drugs and Regimens
Nagasu, Hajime
Yano, Yuichiro
Kanegae, Hiroshi
Heerspink, Hiddo J.L.
Nangaku, Masaomi
Hirakawa, Yosuke
Sugawara, Yuka
Nakagawa, Naoki
Tani, Yuji
Wada, Jun
Sugiyama, Hitoshi
Tsuruya, Kazuhiko
Nakano, Toshiaki
Maruyama, Shoichi
Wada, Takashi
Yamagata, Kunihiro
Narita, Ichiei
Tamura, Kouichi
Yanagita, Motoko
Terada, Yoshio
Shigematsu, Takashi
Sofue, Tadashi
Ito, Takafumi
Okada, Hirokazu
Nakashima, Naoki
Kataoka, Hiromi
Ohe, Kazuhiko
Okada, Mihoko
Itano, Seiji
Nishiyama, Akira
Kanda, Eiichiro
Ueki, Kohjiro
Kashihara, Naoki
Kidney Outcomes Associated With SGLT2 Inhibitors Versus Other Glucose-Lowering Drugs in Real-world Clinical Practice: The Japan Chronic Kidney Disease Database
title Kidney Outcomes Associated With SGLT2 Inhibitors Versus Other Glucose-Lowering Drugs in Real-world Clinical Practice: The Japan Chronic Kidney Disease Database
title_full Kidney Outcomes Associated With SGLT2 Inhibitors Versus Other Glucose-Lowering Drugs in Real-world Clinical Practice: The Japan Chronic Kidney Disease Database
title_fullStr Kidney Outcomes Associated With SGLT2 Inhibitors Versus Other Glucose-Lowering Drugs in Real-world Clinical Practice: The Japan Chronic Kidney Disease Database
title_full_unstemmed Kidney Outcomes Associated With SGLT2 Inhibitors Versus Other Glucose-Lowering Drugs in Real-world Clinical Practice: The Japan Chronic Kidney Disease Database
title_short Kidney Outcomes Associated With SGLT2 Inhibitors Versus Other Glucose-Lowering Drugs in Real-world Clinical Practice: The Japan Chronic Kidney Disease Database
title_sort kidney outcomes associated with sglt2 inhibitors versus other glucose-lowering drugs in real-world clinical practice: the japan chronic kidney disease database
topic Emerging Therapies: Drugs and Regimens
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8546274/
https://www.ncbi.nlm.nih.gov/pubmed/34593566
http://dx.doi.org/10.2337/dc21-1081
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