Department of Endocrinology, Diabetes and Metabolism, Kitasato University School of Medicine, Kanagawa, Japan.
Department of Diagnostic Radiology, Kitasato University School of Medicine, Kanagawa, Japan.
J Diabetes Investig. 2019 Jul;10(4):1004-1011. doi: 10.1111/jdi.12980. Epub 2019 Jan 4.
AIMS/INTRODUCTION: Non-alcoholic fatty liver disease is frequently associated with type 2 diabetes, and constitutes an important risk factor for the development of hepatic fibrosis and hepatocellular carcinoma. Because there remains no effective drug therapy for non-alcoholic fatty liver disease associated with type 2 diabetes, we evaluated the efficacy of sodium-glucose cotransporter 2 inhibitor.
In the present pilot, prospective, non-randomized, open-label, single-arm study, we evaluated the effect of 100 mg canagliflozin administered once daily for 12 months on serological markers, body composition measured by bioelectrical impedance analysis method and hepatic fat fraction measured by magnetic resonance imaging in type 2 diabetes patients with non-alcoholic fatty liver disease.
Canagliflozin significantly reduced body and fat mass, and induced a slight decrease in lean body or muscle mass that did not reach significance at 6 and 12 months. Reductions in fat mass in each body segment (trunk, arms and legs) were evident, whereas those in lean body mass were not. The hepatic fat fraction was reduced from a baseline of 17.6 ± 7.5% to 12.0 ± 4.6% after 6 months and 12.1 ± 6.1% after 12 months (P < 0.0005 and P < 0.005), whereas serum liver enzymes and type IV collagen concentrations improved. From a mean baseline hemoglobin A1c of 8.7 ± 1.4%, canagliflozin significantly reduced hemoglobin A1c after 6 and 12 months to 7.3 ± 0.6% and 7.7 ± 0.7% (P < 0.0005 and P < 0.01).
Canagliflozin reduced body mass, fat mass and hepatic fat content without significantly reducing muscle mass.
目的/引言:非酒精性脂肪性肝病常与 2 型糖尿病相关,是肝纤维化和肝细胞癌发展的重要危险因素。由于目前尚无针对 2 型糖尿病相关非酒精性脂肪性肝病的有效药物治疗方法,我们评估了钠-葡萄糖共转运蛋白 2 抑制剂的疗效。
在本前瞻性、非随机、开放标签、单臂研究中,我们评估了 100mg 卡格列净每日一次给药 12 个月对 2 型糖尿病非酒精性脂肪性肝病患者血清标志物、生物电阻抗分析法测量的身体成分和磁共振成像测量的肝脂肪分数的影响。
卡格列净显著降低了体重和脂肪量,并在 6 个月和 12 个月时引起了瘦体重或肌肉量的轻微下降,但未达到显著水平。各身体部位(躯干、手臂和腿部)的脂肪量减少明显,而瘦体重减少不明显。肝脂肪分数从基线的 17.6±7.5%降至 6 个月时的 12.0±4.6%和 12 个月时的 12.1±6.1%(P<0.0005 和 P<0.005),同时血清肝酶和 IV 型胶原浓度得到改善。卡格列净使平均基线糖化血红蛋白从 8.7±1.4%显著降低至 6 个月时的 7.3±0.6%和 12 个月时的 7.7±0.7%(P<0.0005 和 P<0.01)。
卡格列净降低了体重、脂肪量和肝内脂肪含量,而肌肉量无明显减少。