Effects of canagliflozin, an SGLT2 inhibitor, on hepatic function in Japanese patients with type 2 diabetes mellitus: pooled and subgroup analyses of clinical trials

• Published in: Journal of gastroenterology Vol. 53; no. 1; pp. 140 - 151
• Main Authors: Seko, Yuya, Sumida, Yoshio, Sasaki, Kazuyo, Itoh, Yoshito, Iijima, Hiroaki, Hashimoto, Toshio, Ishii, Shinichi, Inagaki, Nobuya
• Format: Journal Article
• Language: English
• Published: Tokyo Springer Japan 2018; Springer; Springer Nature B.V
• Subjects: Abdominal Surgery; Adult; Aged; Alanine; Alanine transaminase; Antidiabetics; Biliary Tract; Blood Glucose - drug effects; Blood sugar; Body weight; Body Weight - drug effects; Canagliflozin - administration & dosage; Canagliflozin - adverse effects; Canagliflozin - pharmacology; Clinical trials; Colorectal Surgery; Diabetes; Diabetes mellitus; Diabetes Mellitus, Type 2 - drug therapy; Female; Gastroenterology; Glucose; Glycated Hemoglobin A - metabolism; Glycosylated hemoglobin; Hemoglobin; Hepatology; Humans; Hypoglycemic Agents - administration & dosage; Hypoglycemic Agents - adverse effects; Hypoglycemic Agents - pharmacology; Liver; Liver Diseases - drug therapy; Liver Diseases - physiopathology; Liver Function Tests; Male; Medical research; Medicine; Medicine & Public Health; Medicine, Experimental; Middle Aged; Original Article—Liver; Pancreas; Randomized Controlled Trials as Topic; Sodium-Glucose Transporter 2 Inhibitors - administration & dosage; Sodium-Glucose Transporter 2 Inhibitors - adverse effects; Sodium-Glucose Transporter 2 Inhibitors - pharmacology; Surgical Oncology; Type 2 diabetes; Alanine aminotransferase; Type 2 diabetes mellitus; Canagliflozin; Hepatic function; Japan
• ISSN: 0944-1174; 1435-5922
• DOI: 10.1007/s00535-017-1364-8

Background We aimed to investigate the efficacy of canagliflozin (based on its effect on liver function and blood glucose levels) and its safety in high alanine aminotransferase (ALT) patients (ALT >30 U/L). Methods This post hoc analysis of canagliflozin in type 2 diabetes mellitus (T2DM) patients was divided into Study 1 (pooled analysis of 12- and 24-week placebo-controlled, monotherapy studies) and Study 2 (52-week monotherapy/combination therapy study). The canagliflozin 100 mg group data were compared with placebo or baseline ALT subgroup (baseline ALT >30 or ≤30 U/L) data. The primary endpoint was change in ALT level from baseline. Secondary endpoints were changes in efficacy-related parameters. Adverse events (AEs) were evaluated. Results The mean ALT change at 12 weeks was −10.3 ± 11.7 and −3.2 ± 17.6 U/L in the canagliflozin vs. placebo group in the high ALT subgroup ( P  = 0.0206); no significant difference was shown in the low ALT subgroup (Study 1). In both ALT subgroups, glycosylated hemoglobin (HbA1c) and body weight were significantly reduced in the canagliflozin vs. placebo group (all P  < 0.0001). The mean change in ALT at 52 weeks was −16.0 ± 18.8 U/L in the high ALT subgroup ( P  < 0.0001, Study 2). The incidence of AEs or serious AEs in the high ALT subgroup in the canagliflozin group was similar to that in the placebo group (Study 1) or low ALT subgroup (Studies 1 and 2). Conclusions In T2DM patients with impaired liver function, canagliflozin may improve liver function, reduce HbA1c and body weight, and be well tolerated.