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Effectiveness of Ipragliflozin, a Sodium-Glucose Co-transporter 2 Inhibitor, as a Second-line Treatment for Non-Alcoholic Fatty Liver Disease Patients with Type 2 Diabetes Mellitus Who Do Not Respond to Incretin-Based Therapies Including Glucagon-like Peptide-1 Analogs and Dipeptidyl Peptidase-4 Inhibitors

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Abstract

Background

We previously reported that incretin-based drugs, such as dipeptidyl peptidase-4 (DPP-4) inhibitors or glucagon-like peptide-1 (GLP-1) analogs, improved glycemic control and liver inflammation in non-alcoholic fatty liver disease (NAFLD) patients with type 2 diabetes mellitus (T2DM). However, the effect on alanine aminotransferase (ALT) normalization was still limited.

Aims

The aim of this study is to elucidate the effectiveness of sodium-glucose co-transporter 2 (SGLT-2) inhibitors as second-line treatments for NAFLD patients with T2DM who do not respond to incretin-based therapy.

Methods

We retrospectively enrolled 130 consecutive Japanese NAFLD patients with T2DM who were treated with GLP-1 analogs or DPP-4 inhibitors. Among them, 70 patients (53.8 %) had normal ALT levels. Of the remaining 60 patients (46.2 %) who did not have normal ALT levels, 24 (40.0 %) were enrolled in our study and were administered SGLT-2 inhibitors in addition to GLP-1 analogs or DPP-4 inhibitors. We compared changes in laboratory data including ALT levels and body weight at the end of the follow-up.

Results

Thirteen patients were administered a combination of SGLT-2 inhibitors with DPP-4 inhibitors, and the remaining 11 patients were administered a combination of SGLT-2 inhibitors with GLP-1 analogs. The median dosing period was 320 days. At the end of the follow-up, body weight (from 84.8 to 81.7 kg, p < 0.01) and glycosylated hemoglobin levels (from 8.4 to 7.6 %, p < 0.01) decreased significantly. Serum ALT levels also decreased significantly (from 62 to 38 IU/L, p < 0.01) with an improvement in the FIB-4 index (from 1.75 to 1.39, p = 0.04). Finally, 14 patients (58.3 %) achieved normalization of serum ALT levels.

Conclusions

Administration of SGLT-2 inhibitors led to not only good glycemic control, but also to a reduction in body weight, normalization of ALT levels, and a reduction in the FIB-4 index even in patients who did not respond to incretin-based therapy.

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Authors and Affiliations

  1. Department of Gastroenterology, Mitsui Memorial Hospital, 1 Kandaizumicho, Chiyoda-ku, Tokyo, 101-8643, Japan

    Takamasa Ohki, Nobuo Toda & Kazumi Tagawa

  2. Department of Diabetes and Metabolism, Mitsui Memorial Hospital, Tokyo, Japan

    Akihiro Isogawa

Authors
  1. Takamasa Ohki
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  2. Akihiro Isogawa
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  3. Nobuo Toda
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  4. Kazumi Tagawa
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Corresponding author

Correspondence to Takamasa Ohki.

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Contributions

The first author collected all the data and wrote this article. Dr. A. Isogawa, N. Toda, and Dr. K. Tagawa are outpatient clinic doctors who contributed to this study.

Funding

This study received no funding.

Informed consent

Oral informed consent was obtained from all patients when they began treatment but was not required for the present analyses because this was a retrospective study.

Conflict of interest

Takamasa Ohki has received speaking fees from Otsuka Pharmaceutical Co., Ltd. The other authors have nothing to disclose.

Ethical approval

Formal approval was not required for this type of study.

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Ohki, T., Isogawa, A., Toda, N. et al. Effectiveness of Ipragliflozin, a Sodium-Glucose Co-transporter 2 Inhibitor, as a Second-line Treatment for Non-Alcoholic Fatty Liver Disease Patients with Type 2 Diabetes Mellitus Who Do Not Respond to Incretin-Based Therapies Including Glucagon-like Peptide-1 Analogs and Dipeptidyl Peptidase-4 Inhibitors. Clin Drug Investig 36, 313–319 (2016). https://doi.org/10.1007/s40261-016-0383-1

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