Department of Endocrinology, Center for Endocrinology Diabetes Arthritis & Rheumatism (CEDAR) Superspeciality Healthcare, Dwarka, New Delhi, India.
Department of Endocrinology, CEDAR Superspeciality Healthcare, Zirakpur, Punjab, India.
Diabetes Metab Syndr. 2022 Jun;16(6):102539. doi: 10.1016/j.dsx.2022.102539. Epub 2022 Jun 10.
No meta-analysis has analysed efficacy and safety of semaglutide in metabolic-dysfunction associated fatty-liver disease (MAFLD).
Electronic databases were searched for RCTs involving people with MAFLD and/or type-2 diabetes (T2DM) receiving semaglutide. Primary outcome was to evaluate changes in alanine aminotransferase (ALT). Secondary outcomes were to evaluate alterations in other measures of NAFLD, glycaemia, lipids and adverse-events.
Data from 4 RCTs (2115 patients) was analysed. A greater lowering with injectable semaglutide 0.4mg/0.5 mg once weekly was seen with regards to ALT [MD -3.89U/L (95%CI: -5.41 to -2.36); P < 0.01; I = 0%; 2050 patients], liver stiffness (fibroscan®) [MD -3.19 kPa (95%CI: -3.26 to -3.12); P < 0.01; 162 patients], steatosis [MD -13.40 dB/m (95%CI: 20.56 to -6.24); P < 0.01; 162 patients], triglycerides [MD -21.43 mg/dl (95% CI: 41.63 to -1.23); P = 0.04; I = 99%; 2050 patients], total cholesterol [MD -5.53 mg/dl (95% CI: -8.45 to -2.61); P < 0.01; I = 0%; 1888 patients], LDL-cholesterol [MD -3.55 mg/dl (95% CI: -5.87 to -1.23); P < 0.01; I = 0%; 1888 patients], percent-weight [MD -8.99% (95%CI: -14.64 to -3.34); P = 0.002; I = 100%; 2115 patient] and HbA1c [MD -0.77% (95%CI: 1.10 to -0.45); P = 0.002; I = 100%; 2115 patients]. Number of patients inadequate to comment on histopathologic measures of MAFLD. Occurrence of treatment-emergent adverse-events [RR 2.31 (95% CI: 0.76-7.06); P = 0.14; I = 82%] and severe adverse events [RR 1.07 (95%CI: 0.69-1.65); P = 0.77; I = 33%] were comparable. Adverse-events leading to trial discontinuation [RR 2.37 (95% CI: 1.33-4.22); P = 0.003; I = 24%], diarrhea [RR 2.05 (95%CI: 1.17-3.60); P = 0.01; I = 66%], nausea [RR 4.98 (95%CI: 3.23-7.67); P < 0.001; I = 0%] and vomiting [RR 3.90 (95%CI: 1.75-8.68); P < 0.01; I = 54%] were higher with semaglutide.
This meta-analysis provides reassuring data on efficacy of low dose semaglutide injections in improving ALT and certain radiologic features in MAFLD. Current conclusions are limited by small number of patients evaluated. Urgent need remains for larger studies focussing on liver biopsy.
尚无荟萃分析评估司美格鲁肽在代谢功能障碍相关脂肪性肝病（MAFLD）中的疗效和安全性。
检索电子数据库，以评估接受司美格鲁肽治疗的 MAFLD 和/或 2 型糖尿病（T2DM）患者的 RCT。主要结局是评估丙氨酸氨基转移酶（ALT）的变化。次要结局是评估其他非酒精性脂肪性肝病（NAFLD）、血糖、血脂和不良事件的变化。
分析了 4 项 RCT（2115 例患者）的数据。每周一次注射 0.4mg/0.5mg 的司美格鲁肽可更大程度地降低 ALT [MD -3.89U/L（95%CI：-5.41 至 -2.36）；P<0.01；I=0%；2050 例患者]、肝脏硬度（fibroscan®）[MD -3.19kPa（95%CI：-3.26 至 -3.12）；P<0.01；162 例患者]、肝脂肪变性[MD -13.40dB/m（95%CI：20.56 至 -6.24）；P<0.01；162 例患者]、三酰甘油[MD -21.43mg/dl（95%CI：41.63 至 -1.23）；P=0.04；I=99%；2050 例患者]、总胆固醇[MD -5.53mg/dl（95%CI：-8.45 至 -2.61）；P<0.01；I=0%；1888 例患者]、低密度脂蛋白胆固醇[MD -3.55mg/dl（95%CI：-5.87 至 -1.23）；P<0.01；I=0%；1888 例患者]、体重百分比[MD -8.99%（95%CI：-14.64 至 -3.34）；P=0.002；I=100%；2115 例患者]和糖化血红蛋白[MD -0.77%（95%CI：1.10 至 -0.45）；P=0.002；I=100%；2115 例患者]。由于病例数量不足，无法对 MAFLD 的组织病理学指标进行评价。治疗相关不良事件[RR 2.31（95%CI：0.76-7.06）；P=0.14；I=82%]和严重不良事件[RR 1.07（95%CI：0.69-1.65）；P=0.77；I=33%]的发生率无差异。试验中止导致的不良事件[RR 2.37（95%CI：1.33-4.22）；P=0.003；I=24%]、腹泻[RR 2.05（95%CI：1.17-3.60）；P=0.01；I=66%]、恶心[RR 4.98（95%CI：3.23-7.67）；P<0.001；I=0%]和呕吐[RR 3.90（95%CI：1.75-8.68）；P<0.01；I=54%]的发生率较高。
这项荟萃分析提供了令人放心的证据，证明了低剂量司美格鲁肽注射在改善 MAFLD 患者的 ALT 和某些影像学特征方面的疗效。目前的结论受到评估患者数量较少的限制。迫切需要进行专注于肝活检的更大规模研究。
