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Predictors for the Treatment Effect of Sodium Glucose Co-transporter 2 Inhibitors in Patients with Type 2 Diabetes Mellitus

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Abstract

Introduction

Predictors for the effect of sodium glucose co-transporter 2 (SGLT2) inhibitors at lowering hemoglobin A1c (HbA1c) levels in type 2 diabetes mellitus patients remain unclear. We therefore aimed to elucidate these predictors in type 2 diabetes patients after 3 months of SGLT2 treatment.

Methods

A total of 302 consecutive type 2 diabetes patients who had been treated with SGLT2 inhibitors as monotherapy or add-on therapy to existing antidiabetic treatments were enrolled retrospectively. After excluding 27 patients whose HbA1c levels could not be evaluated 3 months after treatment, the glucose-lowering effects of SGLT2 inhibitors were assessed in 275 patients by measuring HbA1c levels before and 3 months after treatment. The predictors for changes in HbA1c levels after 3 months of treatment were evaluated.

Results

SGLT2 inhibitor treatment for 3 months decreased HbA1c levels from 7.8 ± 1.2% to 7.4 ± 1.0% (p < 0.0001). A multiple regression analysis showed that the independent determinants for SGLT2 inhibitor treatment effect included decreased HbA1c levels after 1 month of treatment, high baseline HbA1c levels, and a high estimated glomerular filtration rate (eGFR).

Conclusion

We show that type 2 diabetes patients who received the greatest glucose-lowering effect with SGLT2 inhibitor treatment were those with preserved renal function (high baseline eGFR) and high baseline HbA1c levels. Moreover, SGLT2 inhibitor treatment efficacy could be predicted by the patients’ initial response to treatment.

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Acknowledgements

This work was partially supported by JSPS Kakenhi Grants (Grant numbers 16H05299 and 26248050), GSK Japan Research Grant, The Uehara Memorial Foundation, and Takeda Science Foundation. Article processing charges were funded by the authors. We thank the staff of the Hospital Information Center at Tokushima University Hospital and Masato Mori for extracting clinical data from medical records. We would like to thank Editage (http://www.editage.jp) for English language editing. All named authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship for this manuscript, take responsibility for the integrity of the work as a whole, and have given final approval for the version to be published.

Disclosures

M. Matsuhisa received research funding and lecture fees from Sanofi, Takeda Pharmaceutical Company Ltd., Eli-Lilly, Novo Nordisk Pharma, Astelas Pharma Inc., Boehringer Ingelheim, Daiichi Sankyo Co. Ltd., Tanabe-Mitsubishi Pharma, Novartis Pharmaceuticals Corporation. M. Shimabukuro received research funding from AstraZeneca and lecture fees from Astellas Pharma Inc., Ono Pharmaceutical Company Ltd, Taisho Toyama Pharmaceutical Co., Ltd., Kowa Company, Ltd., Nippon Boehringer Ingelheim, AstraZeneca, and Daiichi Sankyo Co. Ltd. M. Sata received research funding from Tanabe-Mitsubishi, Takeda, Astellas, Bayer Healthcare, Daiichi-Sankyo, MSD, and Ono, and lecture fees from Astellas, Boehringer Ingelheim, Bayer Healthcare, Mochida, Takeda, Tanabe-Mitsubishi, Novartis, AstraZeneca, MSD, and Shionogi. The Department of Cardio-Diabetes Medicine, Tokushima University Graduate School, is supported in part by unrestricted research grants from Actelion, Boehringer Ingelheim, Kowa, and Tanabe-Mitsubishi. Shusuke Yagi, Ken-ichi Aihara, Takeshi Kondo, Kiyoe Kurahashi, Sumiko Yoshida, Itsuro Endo, Daiju Fukuda, Yutaka Nakaya, Kin-ichiro Suwaki, Takashi Takeji, Toshihiro Wada, Hotimah Masdan Salim, Saori Hama, Tomomi Matsuura, Takayuki Ise, Kenya Kusunose, Koji Yamaguchi, Takeshi Tobiume, Hirotsugu Yamada, Takeshi Soeki, Tetsuzo Wakatsuki and Masashi Akaiki have nothing to disclose.

Compliance with Ethics Guidelines

All procedures were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1964, as revised in 2013. The study protocol was approved by the Ethics Committee of Tokushima University Hospital (No. 2432) and Shikoku Central Hospital (No. 25).

Data Availability

The datasets during and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Authors and Affiliations

  1. Department of Cardiovascular Medicine, Tokushima University Graduate School of Biomedical Sciences, Tokushima, Japan

    Shusuke Yagi, Hotimah Masdan Salim, Saori Hama, Tomomi Matsuura, Takayuki Ise, Kenya Kusunose, Koji Yamaguchi, Takeshi Tobiume, Hirotsugu Yamada, Takeshi Soeki, Tetsuzo Wakatsuki & Masataka Sata

  2. Department of Community Medicine and Human Resource Development, Tokushima University Graduate School of Biomedical Sciences, Tokushima, Japan

    Shusuke Yagi

  3. Department of Internal Medicine, Shikoku Central Hospital, Shikokuchuo, Ehime, Japan

    Shusuke Yagi, Yutaka Nakaya, Kin-ichiro Suwaki, Takashi Takeji & Toshihiro Wada

  4. Department of Community Medicine for Diabetes and Metabolic Disorders, Tokushima University Graduate School of Biomedical Sciences, Tokushima, Japan

    Ken-ichi Aihara

  5. Department of Hematology, Endocrinology and Metabolism, Tokushima University Graduate School of Biomedical Sciences, Tokushima, Japan

    Takeshi Kondo, Kiyoe Kurahashi, Sumiko Yoshida & Itsuro Endo

  6. Department of Cardio-Diabetes Medicine, Tokushima University Graduate School of Biomedical Sciences, Tokushima, Japan

    Daiju Fukuda & Michio Shimabukuro

  7. Diabetes Therapeutics and Research Center, Institute of Advanced Medical Sciences, Tokushima University, Tokushima, Japan

    Munehide Matsuhisa

  8. Department of Diabetes, Endocrinology and Metabolism, School of Medicine, Fukushima Medical University, Fukushima, Japan

    Michio Shimabukuro

  9. Department of Medical Education, Tokushima University Graduate School of Biomedical Sciences, Tokushima, Japan

    Masashi Akaike

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  1. Shusuke Yagi
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  2. Ken-ichi Aihara
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  16. Kenya Kusunose
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  19. Hirotsugu Yamada
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  20. Takeshi Soeki
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  21. Tetsuzo Wakatsuki
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  22. Munehide Matsuhisa
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Correspondence to Shusuke Yagi.

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Yagi, S., Aihara, Ki., Kondo, T. et al. Predictors for the Treatment Effect of Sodium Glucose Co-transporter 2 Inhibitors in Patients with Type 2 Diabetes Mellitus. Adv Ther 35, 124–134 (2018). https://doi.org/10.1007/s12325-017-0639-z

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