Effects of Canagliflozin on Hepatic Steatosis, Visceral Fat and Skeletal Muscle among Patients with Type 2 Diabetes and Non-alcoholic Fatty Liver Disease

• Published in: Internal Medicine Vol. 60; no. 21; pp. 3391 - 3399
• Main Authors: Nishimiya, Noriko, Tajima, Kazuki, Imajo, Kento, Kameda, Akiko, Yoshida, Eiko, Togashi, Yu, Aoki, Kazutaka, Inoue, Tomio, Nakajima, Atsushi, Utsunomiya, Daisuke, Terauchi, Yasuo
• Format: Journal Article
• Language: English
• Published: Japan The Japanese Society of Internal Medicine 01-11-2021; Japan Science and Technology Agency
• Subjects: Adipose tissue; Body fat; Body weight; C-reactive protein; Canagliflozin - therapeutic use; Computed tomography; Diabetes; Diabetes mellitus (non-insulin dependent); Diabetes Mellitus, Type 2 - complications; Diabetes Mellitus, Type 2 - drug therapy; Fatty liver; Glucose; Glucose metabolism; Glucose transporter; Hemoglobin; Homeostasis; Humans; imaging; Inflammation; Insulin; Insulin resistance; Internal medicine; Liver - diagnostic imaging; Liver diseases; Magnetic Resonance Imaging; Muscle, Skeletal - diagnostic imaging; Musculoskeletal system; non-alcoholic fatty liver disease; Non-alcoholic Fatty Liver Disease - diagnostic imaging; Non-alcoholic Fatty Liver Disease - drug therapy; Original; Patients; Positron emission tomography; Prospective Studies; Skeletal muscle; sodium-glucose co-transporter type-2 (SGLT2) inhibitor; Steatosis; adipose tissue; non-alcoholic fatty liver disease; skeletal muscle; imaging; sodium-glucose co-transporter type-2 (SGLT2) inhibitor
• ISSN: 0918-2918; 1349-7235; 1349-7235
• DOI: 10.2169/internalmedicine.7134-21

Objective We assessed the effect of canagliflozin, an sodium-glucose co-transporter type-2 inhibitor, on hepatic steatosis using three imaging modalities: magnetic resonance imaging (MRI), computed tomography, and transient elastography. We further determined factors associated with improving hepatic steatosis by canagliflozin among patients with type 2 diabetes and non-alcoholic fatty liver disease (NAFLD). Methods We conducted a six-month prospective single-arm study between August 2015 and June 2017. The primary outcome was the change in hepatic steatosis assessed using the hepatic proton density fat fraction (PDFF) on MRI before and after treatment with canagliflozin. The secondary outcomes were changes in measures of glucose metabolism, including the hepatic glucose uptake on fluorodeoxyglucose-positron emission tomography, and the inflammation and volumes of visceral and subcutaneous adipose tissue and skeletal muscle. Patients Nine patients with type 2 diabetes and NAFLD completed this study. All participants received canagliflozin at a dose of 100 mg daily. Results Canagliflozin caused a significant reduction in hepatic PDFF from baseline [median 20.6% (interquartile range 11.7%, 29.8%)] after 6 months [10.6% (5.4%, 22.6%), p=0.008]. Canagliflozin also significantly reduced the body weight, glycated hemoglobin, homeostasis model assessment of insulin resistance (HOMA-IR), high sensitivity C-reactive protein (hs-CRP), and volumes of adipose tissue and skeletal muscle (all p<0.05). The reduction in hepatic PDFF was not correlated with changes in the body weight, HOMA-IR, hs-CRP, or volume of adipose tissue and skeletal muscle from baseline after six months. Conclusion Among patients with type 2 diabetes and NAFLD, canagliflozin improved hepatic steatosis. The effect may be independent of reducing adiposity, insulin resistance, inflammation, and skeletal muscle volume.