Division of Endocrinology, Diabetes and Metabolism, University of Florida, Gainesville, Florida.
Malcom Randall Veterans Administration Medical Center, Gainesville, Florida.
Diabetes Obes Metab. 2019 Apr;21(4):812-821. doi: 10.1111/dom.13584. Epub 2018 Dec 18.
To evaluate the impact of the sodium glucose co-transporter 2 inhibitor canagliflozin on intrahepatic triglyceride (IHTG) accumulation and its relationship to changes in body weight and glucose metabolism.
In this double-blind, parallel-group, placebo-controlled, 24-week trial subjects with inadequately controlled type 2 diabetes mellitus (T2DM; HbA1c = 7.7% ± 0.7%) from two centres were randomly assigned (1:1) to canagliflozin 300 mg or placebo. We measured IHTG by proton-magnetic resonance spectroscopy (primary outcome), hepatic/muscle/adipose tissue insulin sensitivity during a 2-step euglycaemic insulin clamp, and beta-cell function during a mixed meal tolerance test. Analyses were per protocol.
Between 8 September 2014-13 June 2016, 56 patients were enrolled. Canagliflozin reduced HbA1c (placebo-subtracted change: -0.71% [-1.08; -0.33]) and body weight (-3.4% [-5.4; -1.4]; both P ≤ 0.001). A numerically larger absolute decrease in IHTG occurred with canagliflozin (-4.6% [-6.4; -2.7]) versus placebo (-2.4% [-4.2; -0.6]; P = 0.09). In patients with non-alcoholic fatty liver disease (n = 37), the decrease in IHTG was -6.9% (-9.5; -4.2) versus -3.8% (-6.3; -1.3; P = 0.05), and strongly correlated with the magnitude of weight loss (r = 0.69, P < 0.001). Body weight loss ≥5% with a ≥30% relative reduction in IHTG occurred more often with canagliflozin (38% vs. 7%, P = 0.009). Hepatic insulin sensitivity improved with canagliflozin (P < 0.01), but not muscle or adipose tissue insulin sensitivity. Beta-cell glucose sensitivity, insulin clearance, and disposition index improved more with canagliflozin (P < 0.05).
Canagliflozin improves hepatic insulin sensitivity and insulin secretion and clearance in patients with T2DM. IHTG decreases in proportion to the magnitude of body weight loss, which tended to be greater and occur more often with canagliflozin.
评估钠-葡萄糖共转运蛋白 2 抑制剂卡格列净对肝内甘油三酯（IHTG）蓄积的影响及其与体重和葡萄糖代谢变化的关系。
在这项双盲、平行分组、安慰剂对照、24 周的试验中，来自两个中心的血糖控制不佳的 2 型糖尿病（T2DM；HbA1c=7.7%±0.7%）患者被随机（1:1）分配至卡格列净 300mg 或安慰剂组。我们通过质子磁共振波谱（主要结局）测量 IHTG，通过 2 步正葡萄糖胰岛素钳夹测量肝/肌肉/脂肪组织胰岛素敏感性，通过混合餐耐量试验测量β细胞功能。分析按方案进行。
2014 年 9 月 8 日至 2016 年 6 月 13 日期间，共纳入 56 例患者。与安慰剂相比，卡格列净降低了 HbA1c（安慰剂校正变化：-0.71%[-1.08；-0.33]）和体重（-3.4%[-5.4；-1.4]；均 P≤0.001）。卡格列净组 IHTG 的绝对值下降幅度更大（-4.6%[-6.4；-2.7]），而安慰剂组下降幅度更小（-2.4%[-4.2；-0.6]；P=0.09）。在非酒精性脂肪性肝病（n=37）患者中，IHTG 的下降幅度为-6.9%[-9.5；-4.2]，而安慰剂组为-3.8%[-6.3；-1.3]；P=0.05），与体重减轻的幅度强烈相关（r=0.69，P<0.001）。卡格列净组体重减轻≥5%且 IHTG 相对减少≥30%的患者更多（38% vs. 7%，P=0.009）。卡格列净组肝脏胰岛素敏感性改善（P<0.01），但肌肉或脂肪组织胰岛素敏感性无改善。卡格列净组葡萄糖敏感性、胰岛素清除率和处置指数改善更明显（P<0.05）。
卡格列净可改善 T2DM 患者的肝胰岛素敏感性和胰岛素分泌及清除。IHTG 下降的幅度与体重减轻的幅度成正比，而体重减轻的幅度和出现的频率均与卡格列净相关。
Zotero 插件