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期刊来源：Nat Med

原文链接：https://doi.org/10.1038/s41591-024-03018-2

摘要内容如下：

瑞他鲁肽是一种新型的葡萄糖依赖性促胰岛素多肽、胰高血糖素样肽1和胰高血糖素受体的三重激动剂。一项为期48周的2期肥胖研究显示，服用8毫克和12毫克瑞他鲁肽后，体重分别下降了22.8%和24.2%。该子研究的主要目的是评估该研究中患有代谢功能障碍相关的脂肪变性肝病且肝脏脂肪（LF）≥10%的受试者在24周时的肝脏脂肪（LF）相对于基线的平均相对变化。在该随机、双盲、安慰剂对照试验中，受试者（n=98）被随机分配接受为期48周的每周一次的皮下注射瑞他鲁肽（1、4、8或12mg剂量）或安慰剂。与基线相比，24周时LF的平均相对变化分别为-42.9%（1mg）、-57.0%（4mg）、-81.4%（8mg）、-82.4%（12mg）和+0.3%（安慰剂）（与安慰剂相比，P均<0.001）。在24周时，27%（1mg）、52%（4mg）、79%（8mg）、86%（12mg）和0%（安慰剂）的参与者达到正常LF（<5%）。LF的减少与体重、腹部脂肪和代谢指标的变化显著相关，而代谢指标与胰岛素敏感性和脂质代谢的改善相关。ClinicalTrials.gov注册编号为NCT04881760。

英文原文如下：

Abstracts

Retatrutide is a novel triple agonist of the glucose-dependent insulinotropic polypeptide, glucagon-like peptide 1 and glucagon receptors. A 48-week phase 2 obesity study demonstrated weight reductions of 22.8% and 24.2% with retatrutide 8 and 12 mg, respectively. The primary objective of this substudy was to assess mean relative change from baseline in liver fat (LF) at 24 weeks in participants from that study with metabolic dysfunction-associated steatotic liver disease and ≥10% of LF. Here, in this randomized, double-blind, placebo-controlled trial, participants (n = 98) were randomly assigned to 48 weeks of once-weekly subcutaneous retatrutide (1, 4, 8 or 12 mg dose) or placebo. The mean relative change from baseline in LF at 24 weeks was -42.9% (1 mg), -57.0% (4 mg), -81.4% (8 mg), -82.4% (12 mg) and +0.3% (placebo) (all P < 0.001 versus placebo). At 24 weeks, normal LF (<5%) was achieved by 27% (1 mg), 52% (4 mg), 79% (8 mg), 86% (12 mg) and 0% (placebo) of participants. LF reductions were significantly related to changes in body weight, abdominal fat and metabolic measures associated with improved insulin sensitivity and lipid metabolism. The ClinicalTrials.gov registration is NCT04881760 .

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