title: 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.
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.
  
  
  OBJECTIVE
  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.
authors.affiliation: Department of Gastroenterology, Mitsui Memorial Hospital, 1 Kandaizumicho, Chiyoda-ku, Tokyo, 101-8643, Japan. anb72547@nifty.com.
authors.forename: Takamasa
authors.initials: T
authors.lastname: Ohki
authors.affiliation: Department of Diabetes and Metabolism, Mitsui Memorial Hospital, Tokyo, Japan.
authors.forename: Akihiro
authors.initials: A
authors.lastname: Isogawa
authors.affiliation: Department of Gastroenterology, Mitsui Memorial Hospital, 1 Kandaizumicho, Chiyoda-ku, Tokyo, 101-8643, Japan.
authors.forename: Nobuo
authors.initials: N
authors.lastname: Toda
authors.affiliation: Department of Gastroenterology, Mitsui Memorial Hospital, 1 Kandaizumicho, Chiyoda-ku, Tokyo, 101-8643, Japan.
authors.forename: Kazumi
authors.initials: K
authors.lastname: Tagawa
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000150:complications*; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000627:therapeutic use*; D005260:Female; D052216:Glucagon-Like Peptide 1 / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D005960:Glucosides / Q000627:therapeutic use*; D006801:Humans; D054795:Incretins / Q000627:therapeutic use*; D008103:Liver Cirrhosis / Q000188:drug therapy; D008297:Male; D008875:Middle Aged; D065626:Non-alcoholic Fatty Liver Disease / Q000150:complications / Q000188:drug therapy*; D012189:Retrospective Studies; D051297:Sodium-Glucose Transporter 2; D000077203:Sodium-Glucose Transporter 2 Inhibitors; D013876:Thiophenes / Q000627:therapeutic use*; D015431:Weight Loss / Q000187:drug effects
chemical_list: D054873:Dipeptidyl-Peptidase IV Inhibitors; D005960:Glucosides; D054795:Incretins; C089180:SLC5A2 protein, human; D051297:Sodium-Glucose Transporter 2; D000077203:Sodium-Glucose Transporter 2 Inhibitors; D013876:Thiophenes; C572941:ipragliflozin; D052216:Glucagon-Like Peptide 1; D000410:Alanine Transaminase