Armstrong Matthew J, Okanoue Takeshi, Sundby Palle Mads, Sejling Anne-Sophie, Tawfik Mohamed, Roden Michael
Liver Unit, Queen Elizabeth University Hospital, Birmingham, UK.
National Institute for Health Research, Birmingham Biomedical Research Centre at University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK.
Diabetes Obes Metab. 2025 Feb;27(2):710-718. doi: 10.1111/dom.16065. Epub 2024 Nov 28.
Weight loss mediated by glucagon-like peptide-1 (GLP-1) analogues is lower in patients with type 2 diabetes versus those without. Type 2 diabetes and obesity are risk factors for metabolic dysfunction-associated steatotic liver disease (MASLD) and associated steatohepatitis (MASH). We evaluated weight changes in adults with MASLD/MASH with or without type 2 diabetes receiving the GLP-1 analogue semaglutide.
This was a post hoc analysis of data from three 48-72-week randomised trials investigating the effect of semaglutide versus placebo in adults with MASLD (NCT03357380) or biopsy-confirmed MASH (NCT02970942 and NCT03987451). Pooled data for semaglutide (0.4 mg once daily and 2.4 mg once weekly [n = 163]) and placebo (n = 137) were analysed at 1 year. Weight changes were analysed by type 2 diabetes status (type 2 diabetes [n = 209], pre-type 2 diabetes [n = 51] and no diabetes [n = 40]) and by other cardiometabolic risk parameters using analysis of covariance and Spearman's rank correlations.
The overall mean weight change was -11.1 kg (-11.7%) and -0.7 kg (-0.6%) with semaglutide and placebo, respectively. While numerically higher for people without type 2 diabetes, estimated treatment differences with semaglutide versus placebo were similar overall for people with type 2 diabetes (-10.2 kg; -10.8%), pre-type 2 diabetes (-9.8 kg; -10.2%) and no diabetes (-11.6 kg; -13.1%). Differences between groups were not statistically significant (p > 0.50 for all). Baseline fasting plasma glucose, glycated haemoglobin, insulin levels, insulin resistance and lipids did not correlate with weight change.
People with MASLD/MASH had similar semaglutide-mediated weight loss regardless of type 2 diabetes status and other cardiometabolic risk parameters.
与未患2型糖尿病的患者相比，胰高血糖素样肽-1（GLP-1）类似物介导的体重减轻在2型糖尿病患者中较低。2型糖尿病和肥胖是代谢功能障碍相关脂肪性肝病（MASLD）及相关脂肪性肝炎（MASH）的危险因素。我们评估了接受GLP-1类似物司美格鲁肽的患有或未患有2型糖尿病的成人MASLD/MASH患者的体重变化。
这是一项对三项48 - 72周随机试验数据的事后分析，这些试验研究了司美格鲁肽与安慰剂对患有MASLD的成人（NCT03357380）或经活检证实的MASH患者（NCT02970942和NCT03987451）的影响。在1年时分析了司美格鲁肽（0.4mg每日一次和2.4mg每周一次[n = 163]）和安慰剂（n = 137）的汇总数据。通过2型糖尿病状态（2型糖尿病[n = 209]、糖尿病前期[n = 51]和无糖尿病[n = 40]）以及使用协方差分析和Spearman等级相关性分析其他心脏代谢风险参数来分析体重变化。
司美格鲁肽和安慰剂组的总体平均体重变化分别为-11.1kg（-11.7%）和-0.7kg（-0.6%）。虽然未患2型糖尿病的人在数值上体重减轻更多，但司美格鲁肽与安慰剂相比，2型糖尿病患者（-10.2kg；-10.8%）、糖尿病前期患者（-9.8kg；-10.2%）和无糖尿病患者（-11.6kg；-13.1%）的总体估计治疗差异相似。组间差异无统计学意义（所有p>0.50）。基线空腹血糖、糖化血红蛋白、胰岛素水平、胰岛素抵抗和血脂与体重变化无关。
无论2型糖尿病状态和其他心脏代谢风险参数如何，患有MASLD/MASH的患者经司美格鲁肽介导的体重减轻相似。
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