Non-alcoholic steatohepatitis is frequently associated with diabetes and may cause progressive liver disease. Current treatment options are limited. Here we report on a prospective, randomised, double-blind, placebo-controlled trial of two doses of HTD1801 (berberine ursodeoxycholate, an ionic salt of berberine and ursodeoxycholic acid), versus placebo that was conducted in 100 subjects with fatty liver disease and diabetes (NCT03656744). Treatment was for 18 weeks with a primary endpoint of reduction in liver fat content measured by magnetic resonance imaging proton density fat fraction. Key secondary endpoints included improvement in glycemic control, liver-associated enzymes and safety. The pre-specified primary endpoint was met. Thus, subjects receiving 1000 mg twice a day of berberine ursodeoxycholate had significantly greater reduction in liver fat content than in placebo recipients (mean absolute decrease −4.8% vs. −2.0% (p = 0.011). Compared to placebo, subjects receiving this dose also experienced significant improvement in glycemic control as well as reductions in liver-associated enzymes and significant weight loss. Diarrhea and abdominal discomfort were the most frequently reported adverse events. We conclude that berberine ursodeoxycholate has a broad spectrum of metabolic activity in patients with presumed NASH and diabetes. It is relatively well tolerated and merits further development as a treatment for NASH with diabetes.

非酒精性脂肪性肝炎通常与糖尿病相关，并可能导致进行性肝病。目前的治疗选择有限。在此，我们报告了一项前瞻性、随机、双盲、安慰剂对照试验，在 100 名患有脂肪肝疾病和糖尿病的受试者中进行了两种剂量的 HTD1801（小檗碱熊去氧胆酸盐，小檗碱和熊去氧胆酸的离子盐）与安慰剂的比较（NCT03656744）。治疗持续 18 周，主要终点是通过磁共振成像质子密度脂肪分数测量肝脏脂肪含量减少。主要的次要终点包括血糖控制、肝脏相关酶和安全性的改善。达到了预先指定的主要终点。因此，每天两次服用 1000 mg 熊去氧胆酸小檗碱的受试者比安慰剂接受者的肝脏脂肪含量显着降低（平均绝对下降 -4.8% 与 -2.0% ( p = 0.011)。与安慰剂相比，接受该剂量的受试者血糖控制也显着改善，肝脏相关酶减少，腹泻和腹部不适是最常报告的不良事件。我们得出结论，小檗碱熊去氧胆酸在疑似 NASH 患者中具有广泛的代谢活性。它具有相对良好的耐受性，值得进一步开发作为糖尿病 NASH 的治疗方法。