Nonalcoholic steatohepatitis (NASH) is a common chronic liver disease that may advance to fibrosis and lead to mortality; however, no pharmacotherapy is currently available. We tested the hypothesis that inhibition of both the sodium–glucose cotransporters 1 and 2 with licogliflozin would lead to improvement in NASH. A total of 107 patients with phenotypic or histologic NASH were randomized (1:2:2) to receive oral administration of either placebo (n = 21), licogliflozin 30 mg (n = 43) or 150 mg (n = 43) once daily for 12 weeks. Licogliflozin 150 mg showed a significant 32% (80% confidence interval (CI): 21–43%; P = 0.002) placebo-adjusted reduction in serum alanine aminotransferase after 12 weeks of treatment, the primary endpoint of the study. However, the 30 mg dose of licogliflozin did not meet the primary endpoint (placebo-adjusted reduction 21% (80% CI: 7–32%; P = 0.061)). Diarrhea occurred in 77% (33 of 43), 49% (21 of 43) and 43% (9 of 21) of patients treated with licogliflozin 150 mg, 30 mg and placebo, respectively, which was mostly mild in severity. No other major safety concerns were identified. Treatment with 150 mg licogliflozin led to reductions in serum alanine aminotransferase in patients with NASH. Studies of longer duration and in combination with drugs that have different mechanisms of action are needed to validate these findings and to define a role of licogliflozin as a therapeutic option for NASH. ClinicalTrials.gov identifier: NCT03205150.

非酒精性脂肪性肝炎 (NASH) 是一种常见的慢性肝病，可能会进展为纤维化并导致死亡；然而，目前尚无可用的药物治疗。我们测试了以下假设：用利格列净抑制钠-葡萄糖协同转运蛋白 1 和 2 会改善 NASH。总共 107 名表型或组织学 NASH 患者被随机 (1:2:2) 接受每日一次口服安慰剂 ( n = 21)、利格列净 30 mg ( n = 43) 或 150 mg ( n = 43) 12 周。治疗 12 周后，利格列净 150 mg 经安慰剂调整后血清丙氨酸氨基转移酶显着降低 32%（80% 置信区间 (CI)：21-43%； P = 0.002），这是该研究的主要终点。然而，30 mg 剂量的利格列净未达到主要终点（安慰剂调整后降低 21%（80% CI：7–32%； P = 0.061））。在接受利格列净 150 mg、30 mg 和安慰剂治疗的患者中，腹泻发生率分别为 77%（43 名中的 33 名）、49%（43 名中的 21 名）和 43%（21 名中的 9 名），腹泻的严重程度大多较轻。没有发现其他重大安全问题。 150 mg 利格列净治疗导致 NASH 患者血清丙氨酸氨基转移酶降低。需要进行更长持续时间的研究并与具有不同作用机制的药物相结合来验证这些发现并确定利格列净作为 NASH 治疗选择的作用。 ClinicalTrials.gov 标识符：NCT03205150。