近日，美国休斯顿卫理公会医院Mazen Noureddin团队研究了每周一次培维肽与安慰剂治疗代谢功能障碍相关脂肪性肝炎（IMPACT）的安全性和有效性。相关论文于2025年11月11日发表在《柳叶刀》杂志上。

GLP-1-胰高血糖素双受体激动剂如培维肽在治疗代谢功能障碍相关脂肪性肝炎（MASH）方面显示出前景。该试验旨在评估培维肽在治疗24周后对肝纤维化F2期或F3期MASH患者的MASH消退和纤维化改善的影响。

IMPACT是一项正在进行的为期48周的国际随机、双盲、安慰剂对照的2b期临床试验，在活检证实的MASH和纤维化F2或F3期患者中进行。来自美国和澳大利亚83个机构的患者被随机1:2:2分配，接受每周一次的皮下培维肽（1.2 mg或1.8 mg），不进行剂量滴定或安慰剂。两个主要终点是：在意向治疗人群中，24周时，MASH缓解而无纤维化恶化，或至少一个阶段肝纤维化改善而无MASH恶化。

从2023年7月27日至2025年4月29日，共筛选1557例患者，随机分配212例患者。86例安慰剂组患者中有18例（20%）的MASH消退无纤维化恶化，41例培维肽组患者中有24例（58%）（差异38%；p < 0.001）， 85例培维多肽组患者中有45例（52%）（差异32%；p < 0.001）。86例安慰剂组患者中纤维化改善24例（28%），41例培维肽1.2 mg组患者中13例（33%）（差异为5%，p= 0.59）， 85例培维肽1.8 mg组患者中30例（36%）（差异为8%，p= 0.27）。41例接受1.2 mg培维肽治疗的患者中有32例（78%）报告了不良事件，85例接受1.8 mg培维肽治疗的患者中有69例（81%）报告了不良事件，86例接受安慰剂治疗的患者中有58例（67%）报告了不良事件，其中大多数为轻度或中度严重程度。培维肽耐受性良好，1.2 mg培维肽组41例患者中无一例因不良事件停药，1.8 mg培维肽组85例患者中有1例（1%）停药，安慰剂组86例患者中有2例（2%）停药。

研究结果表明，培维肽治疗在24周时达到了MASH缓解而无纤维化恶化的主要终点，但在该时间点未达到纤维化改善而无MASH恶化的另一个主要终点。计划进行更长时间的其他试验。

附：英文原文

Title: Safety and efficacy of weekly pemvidutide versus placebo for metabolic dysfunction-associated steatohepatitis (IMPACT): 24-week results from a multicentre, randomised, double-blind, phase 2b study

Author: Mazen Noureddin, Stephen A Harrison, Rohit Loomba, Naim Alkhouri, Naga Chalasani, Muhammad Y Sheikh, Shaheen Tomah, Julio A Gutierrez, Silvia Urbina, John J Suschak, Randy Brown, Ozioma Odili, Jay Yang, Stephine Keeton, Guy Neff, Edward Mena, M Scot Roberts, Sarah K Browne, M Scott Harris

Issue&Volume: 2025-11-11

Abstract:

Background

GLP-1–glucagon dual receptor agonists such as pemvidutide have shown promise in treating metabolic dysfunction-associated steatohepatitis (MASH). The aim of this trial was to assess the effects of pemvidutide on MASH resolution and fibrosis improvement in patients with liver fibrosis stage F2 or F3 MASH at 24 weeks of treatment.

Methods

IMPACT is an ongoing 48-week international, randomised, double-blind, placebo-controlled, phase 2b trial in patients with biopsy-confirmed MASH and fibrosis stage F2 or F3. Patients from 83 sites in the USA and Australia were randomly assigned 1:2:2 to receive once-weekly subcutaneous pemvidutide (1·2 mg or 1·8 mg), administered without dose titration, or placebo. The dual primary endpoints were MASH resolution without worsening of fibrosis or at least one stage liver fibrosis improvement without worsening of MASH at 24 weeks in the intention-to-treat population. This trial was registered with ClinicalTrials.gov, NCT05989711.

Findings

From July 27, 2023, to April 29, 2025, 1557 patients were screened and 212 patients were randomly assigned. MASH resolution without fibrosis worsening was observed in 18 (20%) of 86 patients in the placebo group, 24 (58%) of 41 patients in the 1·2 mg pemvidutide group (difference of 38% [95% CI 21–56]; p<0·0001), and 45 (52%) of 85 patients in the 1·8 mg pemvidutide group (difference of 32% [95% CI 19–46]; p<0·0001). Fibrosis improvement without worsening of MASH was observed in 24 (28%) of 86 patients in the placebo group, 13 (33%) of 41 patients in the 1·2 mg pemvidutide group (difference of 5% [95% CI 13 to 22]; p=0·59), and 30 (36%) of 85 patients in the 1·8 mg pemvidutide group (difference of 8% [95% CI 6 to 22]; p=0·27). Adverse events were reported in 32 (78%) of 41 patients receiving 1·2 mg pemvidutide, 69 (81%) of 85 patients receiving 1·8 mg pemvidutide, and 58 (67%) of 86 patients receiving placebo, the majority of which were mild or moderate in severity. Pemvidutide was well tolerated, with discontinuations due to adverse events in none of 41 patients in the 1·2 mg pemvidutide group, one (1%) of 85 patients in the 1·8 mg pemvidutide group, and two (2%) of 86 patients in the placebo group.

Interpretation

Pemvidutide treatment met the primary endpoint of MASH resolution without worsening of fibrosis at 24 weeks but did not meet the other primary endpoint of fibrosis improvement without worsening of MASH at this timepoint. Additional trials of longer duration are planned.

DOI: 10.1016/S0140-6736(25)02114-2

Source: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(25)02114-2/abstract