Pinnacle Clinical Research, San Antonio, TX, USA.
Pinnacle Clinical Research, Austin, TX, USA.
Nat Commun. 2021 Sep 17;12(1):5503. doi: 10.1038/s41467-021-25701-5.
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常与糖尿病相关，并可导致进行性肝病。目前的治疗选择有限。在这里，我们报告了一项前瞻性、随机、双盲、安慰剂对照试验，该试验在 100 名患有脂肪肝和糖尿病的受试者中进行（NCT03656744），比较了两种剂量的 HTD1801（黄连素熊去氧胆酸，黄连素和熊去氧胆酸的离子盐）与安慰剂的疗效。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脂肪含量的减少。关键次要终点包括血糖控制、肝脏相关酶和安全性的改善。预先指定的主要终点达到了。因此，每天接受两次 1000 毫克黄连素熊去氧胆酸治疗的受试者肝脂肪含量的减少明显大于安慰剂组（平均绝对减少-4.8%对-2.0%（p=0.011）。与安慰剂相比，接受该剂量的受试者的血糖控制也显著改善，肝脏相关酶降低，体重显著减轻。腹泻和腹部不适是最常报告的不良事件。我们得出结论，黄连素熊去氧胆酸在患有 NASH 和糖尿病的患者中具有广泛的代谢活性。它具有较好的耐受性，值得进一步开发为治疗伴有糖尿病的 NASH 的药物。
