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Tofogliflozin reduces sleep apnea severity in patients with type 2 diabetes mellitus and heart failure: a prospective study

Hypertension Research volume 48, pages 388–397 (2025)Cite this article

A Comment to this article was published on 16 January 2025

A Comment to this article was published on 20 December 2024

Abstract

Sleep apnea (SA) is prevalent among patients with heart failure (HF) and contributes to a poor prognosis. Sodium–glucose cotransporter 2 (SGLT2) inhibitors have demonstrated efficacy in reducing the risk of serious clinical events in patients with HF. Additionally, SGLT2 inhibitors may reduce the risk of incident SA and mitigate its severity in patients with cardiovascular disease and T2DM. We aimed to investigate whether the SGLT2 inhibitor tofogliflozin reduced the severity of SA, as assessed using the apnea–hypopnea index (AHI), in patients with HF and T2DM and whether a decrease in AHI correlates with changes in body composition and cardiorenal function parameters. This is a single-arm, prospective pathophysiologic study involving patients with HF, T2DM, and SA, defined as having an AHI of 15 events/h and more. SA was assessed using polysomnography. Changes in AHI before and 6 months after starting oral administration of tofogliflozin (20 mg) were assessed. Additionally, body composition and cardiorenal functions were assessed before and 6 months after tofogliflozin administration. Ten patients with HF, T2DM, and SA were finally enrolled (60% men, 66.9 ± 13.4 years). Tofogliflozin reduced AHI from 43.2 [30.2] to 35.3 [13.1] events/h (p = 0.024) at 6 months. Hemoglobin A1c, body weight, and body water content decreased significantly. However, no significant changes were observed in the cardiorenal function parameters. A linear relationship was observed between the changes in body water content and AHI (r = 0.642, p = 0.045). Tofogliflozin reduced AHI, possibly associated with a reduction in body water content.

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Funding

This study was partly supported by JSPS KAKENHI (Grant Numbers, JP21K08116 and JP21K16034) and a Grant-in-Aid for Scientific Research (Grant Numbers, 20FC1027 and 23FC1031) from the Ministry of Health, Labor and Welfare of Japan, a research grant from the Japanese Center for Research on Women in Sport, Juntendo University. These funding sources did not play any other role in this study.

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Authors and Affiliations

  1. Department of Cardiovascular Biology and Medicine, Juntendo University Graduate School of Medicine, Tokyo, Japan

    Sayaki Ishiwata, Takatoshi Kasai, Akihiro Sato, Shoko Suda, Hiroki Matsumoto, Jun Shitara, Shoichiro Yatsu, Azusa Murata, Megumi Shimizu, Takao Kato, Masaru Hiki, Ryo Naito, Katsumi Miyauchi, Hiroyuki Daida & Tohru Minamino

  2. Cardiovascular Respiratory Sleep Medicine, Juntendo University Graduate School of Medicine, Tokyo, Japan

    Sayaki Ishiwata, Takatoshi Kasai, Akihiro Sato, Mitsue Kato, Fusae Kawana & Ryo Naito

  3. Sleep and Sleep-Disordered Breathing Center, Juntendo University Hospital, Tokyo, Japan

    Sayaki Ishiwata, Takatoshi Kasai, Shoko Suda & Ryo Naito

  4. Department of Cardiovascular Management and Remote Monitoring, Juntendo University Graduate School of Medicine, Tokyo, Japan

    Takatoshi Kasai & Shiroshita Nanako

  5. Faculty of Health Science, Juntendo University, Tokyo, Japan

    Hiroyuki Daida

  6. Japan Agency for Medical Research and Development-Core Research for Evolutionary Medical Science and Technology (AMED-CREST), Japan Agency for Medical Research and Development, Tokyo, Japan

    Tohru Minamino

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  1. Sayaki Ishiwata
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  2. Takatoshi Kasai
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Contributions

SI contributed to the study. SI and TK contributed to the study design. AS, SS, HM, JS, SY, AM, MS, TK, MH, SN, MK, and FK collected data. SI, RN, KM, and TK performed data and statistical analyses. SI and TK drafted the manuscript. SI, TK, AS, SS, HM, JS, SY, AM, MS, TK, MH, SN, MK, and FK performed critical revision, editing, and approval of the final manuscript. SI, TK, HD, and TM are responsible for the overall content of guarantors.

Corresponding author

Correspondence to Takatoshi Kasai.

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Conflict of interest

SI and T Kasai contributed to the study design. AS, SS, HM, JS, SY, AM, MS, T Kato, MH, SN, MK, and FK collected data. SI, RN, KM, and T Kasai performed data and statistical analyses. SI and T Kasai drafted the manuscript. SI, T Kasai, AS, SS, HM, JS, SY, AM, MS, T Kato, MH, SN, MK, and FK performed critical revision, editing, and approval of the final manuscript. SI, T Kasai, HD, and TM are responsible for the overall content of guarantors

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Ishiwata, S., Kasai, T., Sato, A. et al. Tofogliflozin reduces sleep apnea severity in patients with type 2 diabetes mellitus and heart failure: a prospective study. Hypertens Res 48, 388–397 (2025). https://doi.org/10.1038/s41440-024-01982-3

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