Division of Diabetes, Metabolism, and Endocrinology, Department of Medicine, Toho University Graduate School of Medicine, Tokyo, Japan.
Department of Diabetology and Endocrinology, Kanazawa Medical University, Ishikawa, Japan.
Diabetes Obes Metab. 2023 Jun;25(6):1576-1588. doi: 10.1111/dom.15006. Epub 2023 Feb 21.
To compare the effects of sodium-glucose co-transporter-2 (SGLT2) inhibitors and dipeptidyl peptidase-4 inhibitors on ectopic fat accumulation and tissue-specific insulin sensitivity.
This randomized controlled trial enrolled 44 patients with type 2 diabetes (T2D) and non-alcoholic fatty liver disease (NAFLD). They were randomly assigned to receive either empagliflozin 10 mg/day or sitagliptin 100 mg/day for 12 weeks. The primary endpoint was the change in intrahepatic lipid content (IHL) measured using proton magnetic resonance spectroscopy ( H-MRS). The secondary endpoints included intramuscular and extramuscular lipid content seen in H-MRS, body composition seen through dual-energy X-ray absorptiometry and tissue-specific insulin sensitivity shown through hyperinsulinaemic-euglycaemic clamp using stable isotopic glucose. Liver biopsy samples were pathologically evaluated at baseline.
At baseline, the mean duration of diabetes, HbA1c level and IHL were 3.7 years, 7.2% and 20.9%, respectively. The median NAFLD activity score was 3.0. IHL was significantly more decreased in the empagliflozin group than that in the sitagliptin group (between-group difference was -5.2% ± 1.1% and -1.9% ± 1.2%, respectively, (95% confidence interval); -3.3 (-6.5, -0.1), P = .044). However, there were no significant between-group differences in the change of insulin sensitivity in the liver, muscle or adipose tissues. Interestingly, hepatic insulin sensitivity was significantly increased only in the empagliflozin group and was significantly negatively associated with the change in IHL.
Empagliflozin significantly improves hepatic steatosis compared with sitagliptin, and this may protect against subsequent hepatic insulin resistance. Early administration of SGLT2 inhibitors is preferable for T2D patients with NAFLD.
比较钠-葡萄糖共转运蛋白 2（SGLT2）抑制剂和二肽基肽酶-4（DPP-4）抑制剂对异位脂肪堆积和组织特异性胰岛素敏感性的影响。
本随机对照试验纳入了 44 例 2 型糖尿病（T2D）合并非酒精性脂肪性肝病（NAFLD）患者。他们被随机分为恩格列净 10mg/天或西格列汀 100mg/天组，治疗 12 周。主要终点是使用质子磁共振波谱（H-MRS）测量的肝内脂质含量（IHL）的变化。次要终点包括 H-MRS 观察到的肌内和肌外脂质含量、双能 X 射线吸收法测量的身体成分和使用稳定同位素葡萄糖的高胰岛素-正葡萄糖钳夹试验测量的组织特异性胰岛素敏感性。基线时进行肝活检病理评估。
基线时，糖尿病病程、HbA1c 水平和 IHL 的平均值分别为 3.7 年、7.2%和 20.9%。中值 NAFLD 活动评分 3.0。与西格列汀组相比，恩格列净组 IHL 降低更明显（组间差异分别为-5.2%±1.1%和-1.9%±1.2%，95%置信区间；-3.3[-6.5，-0.1]，P=0.044）。然而，两组间肝脏、肌肉或脂肪组织胰岛素敏感性的变化无显著差异。有趣的是，仅恩格列净组肝胰岛素敏感性显著增加，且与 IHL 变化显著负相关。
与西格列汀相比，恩格列净显著改善肝脂肪变性，这可能有助于预防后续的肝胰岛素抵抗。对于合并 NAFLD 的 T2D 患者，早期应用 SGLT2 抑制剂更优。
