目的:评价口服司马鲁肽治疗2型糖尿病(T2DM)合并代谢功能障碍相关脂肪变性肝病(MASLD)的疗效和安全性。
方法:这是单臂,多中心,前瞻性研究。在80例连续接受新口服司马鲁肽的MASLD和T2DM患者中,70人按计划完成了为期48周的口服司马鲁肽治疗,并纳入疗效分析。每位医师在监测疗效和不良事件的同时确定口服司马鲁肽的剂量调整。
结果:体重显著改善,肝酶,血脂谱,与基线值相比,在48周时发现血糖控制(所有p<0.01)。对照衰减参数值从基线到48周显著降低(p<0.01)。丙氨酸转氨酶浓度的变化(r=0.37,p<0.01)和受控衰减参数值(r=0.44,p<0.01)与体重变化显着相关。肝纤维化标志物,如IV型胶原蛋白7S,紫藤凝集素阳性Mac-2结合蛋白,纤维化-4指数,和肝脏硬度测量,从基线到48周显着降低(所有p<0.01)。最常见的不良事件是1-2级短暂性胃肠道症状,如恶心(23名患者,28.8%),消化不良(12,15.0%)和食欲减退(4,5.0%)。
结论:口服司马鲁肽治疗2型糖尿病MASLD患者可改善肝脏脂肪变性和损伤,纤维化的替代标志物,糖尿病状态,和脂质分布,减轻体重。
OBJECTIVE: To evaluate the efficacy and safety of oral semaglutide for type 2 diabetes mellitus (T2DM) in patients with metabolic dysfunction-associated steatotic liver disease (MASLD).
METHODS: This was a single-arm, multicentre, prospective study. Among 80 consecutive patients with MASLD and T2DM who newly received oral semaglutide, 70 completed 48-week oral semaglutide treatment as scheduled and were included in an efficacy analysis. Dose adjustments of oral semaglutide were determined by each physician while monitoring efficacy and adverse events.
RESULTS: Significant improvements in body weight, liver enzymes, lipid profile, and glycaemic control were found at 48 weeks compared with baseline values (all p < 0.01). Controlled attenuation parameter values significantly decreased from baseline to 48 weeks (p < 0.01). Changes in alanine aminotransferase concentrations (r = 0.37, p < 0.01) and controlled attenuation parameter values (r = 0.44, p < 0.01) were significantly correlated with changes in body weight. Liver fibrosis markers, such as type IV collagen 7S, Wisteria floribunda agglutinin-positive Mac-2-binding protein, fibrosis-4 index, and liver stiffness measurement, significantly decreased from baseline to 48 weeks (all p < 0.01). The most common adverse events were Grades 1-2 transient gastrointestinal symptoms, such as nausea (23 patients, 28.8%), dyspepsia (12, 15.0%) and appetite loss (4, 5.0%).
CONCLUSIONS: Oral semaglutide treatment for T2DM in patients with MASLD leads to an improvement in liver steatosis and injury, surrogate markers of fibrosis, diabetic status, and lipid profile, and reduces body weight.