900 Hospital of the Joint Logistics Team, Fuzong Clinical Medical College of Fujian Medical University, Fuzhou 365000, Fujian, China.
900 Hospital of the Joint Logistics Team, Fuzong Clinical Medical College of Fujian Medical University, Fuzhou 365000, Fujian, China.
Diabetes Res Clin Pract. 2020 Dec;170:108487. doi: 10.1016/j.diabres.2020.108487. Epub 2020 Oct 6.
Type 2 diabetes mellitus is closely related to nonalcoholic fatty liver disease(NAFLD). More and more attention has been paid to the efficacy of liraglutide in the treatment of NAFLD, but the clinical evidence is still insufficient.
The purpose of this study was to use proton magnetic resonance spectroscopy (H-MRS) assessment of metformin alone poor blood glucose control of obese patients type 2 diabetes with NAFLD, added with insulin glargine, liraglutide or placebo effect in improving the fatty liver.
This is a 26-week, single-center, prospective, randomized placebo-controlled study. From September 2016 to July 2018, 128 patients with type 2 diabetes and NAFLD were enrolled in the China joint logistics team 900 hospital. The primary endpoints were the changes in intrahepatic content of lipid (IHCL), abdominal adiposity [subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT)], from baseline to week 26 (end of treatment) and the changes in liraglutide group or insulin glargine group versus change in placebo group. Secondary endpoints included the changes in liver function (AST and ALT), glycemia (HbA1c and FPG), body weight, and BMI.
A total of 96 patients with type 2 diabetes and NAFLD under inadequate glycemic control by metformin were randomized (1:1:1) to receive add-on insulin glargine, liraglutide, or placebo. After 26 weeks of treatment, compared to the placebo group, in the liraglutide and insulin glargine groups, IHCL significantly decreased from baseline to week 26 (liraglutide 26.4% ± 3.2% to 20.6% ± 3.9%, P < 0.05; insulin glargine 25.0% ± 4.3% to 22.6% ± 5.8%, P > 0.05). SAT and VAT decreased significantly in the liraglutide group and in the insulin glargine group (P < 0.05). ΔSAT and ΔVAT were greater with liraglutide than insulin glargine, they were significantly different between the two groups (ΔSAT, -36 vs. - 24.5, P < 0.05; and ΔVAT, -47 vs. - 16.6, P > 0.05). In the liraglutide group, AST, ALT, and HOMA-IR decreased significantly from baseline. There was no significant difference in glucose-lowering among the three groups. During the treatment, the safety of the three groups performed well.
Compared with placebo, treatment with liraglutide plus an adequate dose of metformin (2000 g/ day) for 26 weeks is more effective in reducing IHCL, SAT and VAT in patients with type 2 diabetes and NAFLD. And it has additional advantages in weight loss, waist circumference reduction and liver function improvement.
2 型糖尿病与非酒精性脂肪性肝病（NAFLD）密切相关。越来越多的人关注利拉鲁肽治疗 NAFLD 的疗效，但临床证据仍不足。
本研究旨在使用质子磁共振波谱（H-MRS）评估二甲双胍血糖控制不佳的肥胖 2 型糖尿病合并 NAFLD 患者，加用胰岛素 glargine、利拉鲁肽或安慰剂对改善脂肪肝的效果。
这是一项 26 周、单中心、前瞻性、随机安慰剂对照研究。2016 年 9 月至 2018 年 7 月，共纳入 128 例中国联合后勤部队 900 医院的 2 型糖尿病合并 NAFLD 患者。主要终点为基线至治疗 26 周（治疗结束）时肝内脂质含量（IHCL）、腹部脂肪（皮下脂肪组织[SAT]和内脏脂肪组织[VAT]）的变化，以及利拉鲁肽组或胰岛素 glargine 组与安慰剂组的变化。次要终点包括肝功能（AST 和 ALT）、血糖（HbA1c 和 FPG）、体重和 BMI 的变化。
共 96 例二甲双胍血糖控制不佳的 2 型糖尿病合并 NAFLD 患者被随机分为（1:1:1）接受胰岛素 glargine、利拉鲁肽或安慰剂加用。经过 26 周的治疗，与安慰剂组相比，利拉鲁肽和胰岛素 glargine 组的 IHCL 从基线到 26 周显著降低（利拉鲁肽组 26.4%±3.2%降至 20.6%±3.9%，P<0.05；胰岛素 glargine 组 25.0%±4.3%降至 22.6%±5.8%，P>0.05）。利拉鲁肽组和胰岛素 glargine 组的 SAT 和 VAT 均显著降低（P<0.05）。利拉鲁肽组的 ΔSAT 和 ΔVAT 大于胰岛素 glargine 组，两组间差异有统计学意义（ΔSAT，-36 比-24.5，P<0.05；ΔVAT，-47 比-16.6，P>0.05）。利拉鲁肽组治疗后 AST、ALT 和 HOMA-IR 均显著降低。三组间降糖效果无显著差异。三组治疗期间安全性均良好。
与安慰剂相比，26 周的利拉鲁肽联合二甲双胍（2000g/天）治疗可更有效降低 2 型糖尿病合并 NAFLD 患者的 IHCL、SAT 和 VAT，且在体重减轻、腰围缩小和肝功能改善方面具有额外优势。
