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Real-world evidence for long-term safety and effectiveness of ipragliflozin in treatment-naïve versus non-naïve Japanese patients with type 2 diabetes mellitus: subgroup analysis of a 3-year post-marketing surveillance study (STELLA-LONG TERM)

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Abstract

Background

STELLA-LONG TERM was a 3-year post-marketing surveillance study that evaluated the long-term safety and effectiveness of ipragliflozin in Japanese patients with type 2 diabetes mellitus (T2DM). This subgroup analysis examined the safety and effectiveness of ipragliflozin in treatment-naïve and non-naïve patients.

Materials and methods

Patients were stratified into two subgroups: treatment-naïve (patients who had not received any antidiabetic drugs before starting ipragliflozin monotherapy) and non-naïve (all other patients). Patients who had added or switched antidiabetic drugs during follow-up were excluded from the analysis from that point. The incidence of adverse drug reactions (ADRs) and changes from baseline in glycosylated hemoglobin (HbA1c), body weight, fasting plasma glucose (FPG) and laboratory parameters were assessed.

Results

Of the 11,051 patients in the safety analysis set, 1980 patients (17.92%) were treatment-naïve and 9071 (82.08%) were non-naïve. In the safety analysis set, treatment-naïve patients reported significantly lower incidences of ADRs (10.81% vs 20.87%; p < 0.001) and serious ADRs (0.86% vs 2.09%; p < 0.001) compared with non-naïve patients, as well as significantly lower incidences of polyuria/pollakiuria, volume depletion-related events, skin complications and renal disorders. In the effectiveness analysis, sustained and significant reductions from baseline to 36 months were observed in HbA1c, FPG and body weight in both treatment-naïve and non-naïve patients (all p < 0.001 vs baseline).

Conclusions

Over 3 years, ipragliflozin was better tolerated in treatment-naive than in non-naive Japanese patients with T2DM and had similar efficacy in these populations. Therefore, ipragliflozin is a useful first-line treatment option for patients with T2DM.

Clinical trial registration

ClinicalTrials.gov: NCT02479399.

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Acknowledgements

The authors thank all the participants in this study. Medical writing support was provided by Catherine Rees and Sarah Greig, PhD, of inScience Communications, Springer Healthcare; this medical writing support was funded by Astellas Pharma Inc.

Funding

This study was funded by Astellas Pharma Inc.

Author information

Authors and Affiliations

  1. Department of Medicine, Shiga University of Medical Science, Seta-tsukinowa-cho, Otsu, Shiga, 520-2192, Japan

    Hiroshi Maegawa

  2. First Department of Internal Medicine, Graduate School of Medicine and Pharmaceutical Sciences for Research, University of Toyama, Toyama, Japan

    Kazuyuki Tobe

  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. Hiroshi Maegawa
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Corresponding author

Correspondence to Hiroshi Maegawa.

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Conflict of interest

HM received lecture fees from MSD K.K., Nippon Boehringer Ingelheim Co. Ltd., Mitsubishi Tanabe Pharma Corporation, Sanofi K.K., Astellas Pharma Inc., Takeda Pharmaceutical Co. Ltd., Kowa Pharmaceutical Co. Ltd., Daiichi Sankyo Co. Ltd., Novo Nordisk Pharma Ltd., Eli Lilly Japan K.K. and Kissei Pharmaceutical Co. Ltd.; research support from Astellas Pharma Inc., Astra Zeneca K.K., Nippon Boehringer Ingelheim Co. Ltd., Sunstar Inc., Mitsubishi Tanabe Pharma Corporation, Kyowa Hakko 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., Kyowa Hakko Kirin Co. Ltd., Taisho Pharma Co. Ltd., Kowa Pharmaceutical Co. Ltd., Ono Pharmaceutical Co. Ltd., Daiichi Sankyo Co. Ltd., Sanofi K.K., Mitsubishi Tanabe Pharma Corporation, Sanwa Kagaku Kenkyusho Co. Ltd., Eli Lilly Japan K.K., Sumitomo Dainippon Pharma Co. Ltd., Novo Nordisk Pharma Ltd., Bayer Yakuhin Ltd., Teijin Pharma Limited, Shionogi & Co. Ltd., Fuji Yakuhin Co. Ltd., Pfizer Inc., MIKI Corporation, Mochida Pharmaceutical Co. Ltd., Novartis Pharma K.K. and Nipro Corporation. KT 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. IN and SU are employees of Astellas Pharma Inc.

Human rights statement and informed consent

This study was conducted in compliance with Japanese Good Post-marketing Study Practice (GPSP) regulations. Under these regulations, informed consent was not necessary because the study involved anonymized data collected from clinical settings.

Data sharing statement

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

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Maegawa, H., Tobe, K., Nakamura, I. et al. Real-world evidence for long-term safety and effectiveness of ipragliflozin in treatment-naïve versus non-naïve Japanese patients with type 2 diabetes mellitus: subgroup analysis of a 3-year post-marketing surveillance study (STELLA-LONG TERM). Diabetol Int 12, 430–444 (2021). https://doi.org/10.1007/s13340-021-00501-w

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