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Safety and effectiveness of ipragliflozin in Japanese patients with type 2 diabetes mellitus and impaired renal function: subgroup analysis of a 3-year post-marketing surveillance study (STELLA-LONG TERM)

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Abstract

STELLA-LONG TERM, a 3-year post-marketing surveillance study, evaluated the safety and effectiveness of the sodium-glucose cotransporter 2 inhibitor ipragliflozin in Japanese type 2 diabetes mellitus (T2DM) patients. Final results in the safety (n = 6697) and effectiveness populations (n = 5625) were analyzed by stratifying patients by baseline estimated glomerular filtration rate (eGFR, mL/min/1.73 m2) into four subgroups (≥ 90, 60 to < 90, 45 to < 60, and < 45) and two subgroups (≥ 60 and < 60). Adverse drug reaction (ADR) incidence, and changes from baseline in glycosylated hemoglobin (HbA1c), bodyweight, and eGFR were assessed. The percentage of patients experiencing ADRs and serious ADRs was similar across most eGFR subgroups. Polyuria/pollakiuria was the most common ADR. Renal disorders and volume depletion ADRs were more frequent in the subgroups with more severe renal impairment at baseline than in those with an eGFR of 60 to < 90 or ≥ 90 mL/min/1.73 m2. Bodyweight and HbA1c decreased in all subgroups, the latter by − 0.91% to − 0.40% (P < 0.05 vs. baseline). eGFR increased in the 45 to < 60 mL/min/1.73 m2 subgroup (+ 1.42 ± 8.77 mL/min/1.73 m2; P = 0.006). It decreased in the ≥ 90 and 60 to < 90 mL/min/1.73 m2 subgroups (− 8.27 ± 13.73 and − 1.22 ± 10.34 mL/min/1.73 m2; P < 0.001), but not to < 60 mL/min/1.73 m2. In conclusion, there were no new or unexpected safety findings in Japanese patients treated with ipragliflozin for T2DM, and long-term sustained improvements in HbA1c and bodyweight were observed regardless of the presence of renal impairment.

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Acknowledgements

The authors thank all the participants in this study. This study was funded by Astellas Pharma Inc. Medical writing support was provided by Atsuko Yamazaki, PhD, and Tracy Harrison, of inScience Communications, Springer Healthcare, and was funded by Astellas Pharma Inc.

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Authors and Affiliations

  1. First Department of Internal Medicine, Graduate School of Medicine and Pharmaceutical Sciences for Research, University of Toyama, 2630 Sugitani, Toyama, 930-0194, Japan

    Kazuyuki Tobe

  2. Department of Medicine, Shiga University of Medical Science, Shiga, Japan

    Hiroshi Maegawa

  3. Operational Excellence, Medical Affairs Japan, Astellas Pharma Inc., Tokyo, Japan

    Ichiro Nakamura

  4. Data Science, Development, Astellas Pharma Inc., Tokyo, Japan

    Satoshi Uno

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  1. Kazuyuki Tobe
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Contributions

TK, MH and US contributed to the study design, data analysis and data interpretation. NI contributed to the study design, study conduct, data collection, data analysis and data interpretation. All authors contributed to writing the manuscript and approved the final draft for submission.

Corresponding author

Correspondence to Kazuyuki Tobe.

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Conflict of interest

Tobe K received lecture fees from MSD K.K., Novo Nordisk Pharma Ltd., Kowa Pharmaceutical Co. Ltd.; grants from Daiichi Sankyo Co. Ltd., Ono Pharmaceutical Co. Ltd., Takeda Pharmaceutical Co. Ltd., Nippon Boehringer Ingelheim Co. Ltd., MSD K.K., Mitsubishi Tanabe Pharma Corporation, Teijin Pharma Limited, Eli Lilly Japan K.K., Asahi Kasei Pharma Corporation, The Mitsubishi Foundation, and Suntory Global Innovation Center Ltd. Maegawa H has received lecture fees from MSD K.K., Sanofi K.K., Astellas Pharma Inc., Nippon Boehringer Ingelheim Co. Ltd., Takeda Pharmaceutical Co. Ltd., Mitsubishi Tanabe Pharma Corporation, Daiichi Sankyo Co. Ltd., Astra Zeneca K.K., Eli Lilly Japan K.K., Novo Nordisk Pharma Ltd. and Sumitomo Dainippon Pharma Co. Ltd.; research support from Astellas Pharma Inc., Astra Zeneca K.K., Nippon Boehringer Ingelheim Co. Ltd., Sunstar Inc., Mitsubishi Tanabe Pharma Corporation, Kyowa Kirin Co. Ltd., Nissan Chemical Corporation and MIKI Corporation; grants from Takeda Pharmaceutical Co. Ltd., Astellas Pharma Inc., MSD K.K., Nippon Boehringer Ingelheim Co. Ltd., Mitsubishi Tanabe Pharma Corporation, Daiichi Sankyo Co. Ltd., Sumitomo Dainippon Pharma Co. Ltd., Kowa Pharmaceutical Co. Ltd., Taisho Pharma Co. Ltd., Ono Pharmaceutical Co. Ltd., Sanofi K.K., Sanwa Kagaku Kenkyusho Co. Ltd., Eli Lilly Japan K.K., Novo Nordisk Pharma Ltd., Bayer Yakuhin Ltd., Teijin Pharma Limited, Shionogi & Co. Ltd., Novartis Pharma K.K. and Nipro Corporation. Nakamura I and Uno S are employees of Astellas Pharma Inc.

Ethical standards and human rights statement

This study was conducted as a special drug use surveillance study in compliance with Japanese Good Post-marketing Study Practice (GPSP) and the study protocol was approved by the Japanese government Ministry of Health, Labour and Welfare. All medical institutions that agreed to provide data signed a contract with Astellas Pharma Inc.

Informed consent

Anonymous patient data were collected via electronic survey forms from clinical settings, thus it was not deemed necessary to obtain patient informed consent.

Data sharing statement

Researchers may request access to anonymized participant level data, trial level data and protocols from Astellas sponsored clinical trials at www.clinicalstudydatarequest.com. For the Astellas criteria on data sharing see: https://clinicalstudydatarequest.com/Study-Sponsors/Study-Sponsors-Astellas.aspx

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Tobe, K., Maegawa, H., Nakamura, I. et al. Safety and effectiveness of ipragliflozin in Japanese patients with type 2 diabetes mellitus and impaired renal function: subgroup analysis of a 3-year post-marketing surveillance study (STELLA-LONG TERM). Diabetol Int 12, 181–196 (2021). https://doi.org/10.1007/s13340-020-00470-6

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