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利格列净治疗非酒精性脂肪性肝炎的随机对照研究
作者:小柯机器人 发布时间:2022/6/26 0:34:57

美国Pinnacle临床研究公司Stephen A. Harrison团队近期取得重要工作进展,他们对利格列净药物治疗非酒精性脂肪性肝炎进行了一项随机、双盲、安慰剂对照的2a期研究。该项研究成果2022年6月20日在线发表于《自然—医学》杂志上。

研究人员测试了这样的假设:用利格列净抑制钠-葡萄糖共转运体1和2会导致NASH的改善。共有107名表型或组织学NASH患者被随机分配(1:2:2)接受安慰剂(n = 21)、利格列净30mg (n = 43) 或 150 mg (n = 43) 每日一次口服给药12周。 利格列净150毫克显示,治疗12周后,经安慰剂调整后,血清丙氨酸氨基转移酶显著降低32%(80%置信区间(CI):21-43%;P = 0.002),这是研究的主要终点。

然而,30 mg 剂量的利格列净未达到主要终点(安慰剂调整后减少21%(80% CI:7-32%;P = 0.061))。利格列净150 mg、30 mg和安慰剂治疗的患者分别有 77%(43 人中的 33 人)、49%(43 人中的21人)和43%(21人中的9人)发生腹泻,其严重程度大多为轻度。没有发现其他重大安全问题。用150 mg利格列净治疗可降低NASH患者的血清丙氨酸氨基转移酶。需要进行更长时间的研究并结合具有不同作用机制的药物来验证这些发现并确定利格列净作为NASH治疗选择的作用。

据介绍,非酒精性脂肪性肝炎(NASH)是一种常见的慢性肝病,可发展为纤维化并导致死亡;然而,目前还没有药物疗法可用。

附:英文原文

Title: Licogliflozin for nonalcoholic steatohepatitis: a randomized, double-blind, placebo-controlled, phase 2a study

Author: Harrison, Stephen A., Manghi, Federico Perez, Smith, William B., Alpenidze, Diana, Aizenberg, Diego, Klarenbeek, Naomi, Chen, Chi-Yi, Zuckerman, Eli, Ravussin, Eric, Charatcharoenwitthaya, Phunchai, Cheng, Pin-Nan, Katchman, Helena, Klein, Samuel, Ben-Ari, Ziv, Mendonza, Anisha E., Zhang, Yiming, Martic, Miljen, Ma, Shenglin, Kao, Sheena, Tanner, Sandra, Pachori, Alok, Badman, Michael K., He, YanLing, Ukomadu, Chinweike, Sicard, Eric

Issue&Volume: 2022-06-20

Abstract: 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 30mg (n=43) or 150mg (n=43) once daily for 12 weeks. Licogliflozin 150mg 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 30mg 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 150mg, 30mg and placebo, respectively, which was mostly mild in severity. No other major safety concerns were identified. Treatment with 150mg 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.

DOI: 10.1038/s41591-022-01861-9

Source: https://www.nature.com/articles/s41591-022-01861-9

期刊信息

Nature Medicine:《自然—医学》,创刊于1995年。隶属于施普林格·自然出版集团,最新IF:30.641
官方网址:https://www.nature.com/nm/
投稿链接:https://mts-nmed.nature.com/cgi-bin/main.plex