Wu Jheng-Yan, Hsu Wan-Hsuan, Kuo Chia-Chih, Tsai Ya-Wen, Liu Ting-Hui, Huang Po-Yu, Chuang Min-Hsiang, Hung Kuo-Chuan, Yu Tsung, Lai Chih-Cheng
Department of Nutrition, Chi Mei Medical Center, Tainan, Taiwan.
Department of Public Health, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
Nat Commun. 2025 Aug 12;16(1):7459. doi: 10.1038/s41467-025-62891-8.
The impact of adding glucagon-like peptide-1 receptor agonists (GLP-1RAs) to sodium-glucose co-transporter-2 inhibitors (SGLT2is) for metabolic dysfunction-associated steatotic liver disease (MASLD) is unclear. This retrospective study compared the effect of GLP-1RA plus SGLT2i versus SGLT2i alone for MASLD. Combination therapy was associated with a lower risk of primary composite outcomes of all-cause hospitalization, all-cause mortality, major adverse cardiovascular events (MACE), major adverse kidney events (MAKE), and major adverse liver outcomes (MALO) (hazard ratio [HR], 0.87; 95% confidence interval [CI], 0.84-0.91). Combination therapy also showed lower risks for all-cause hospitalization (HR, 0.86; 95% CI, 0.82-0.90), all-cause mortality (HR, 0.45; 95% CI, 0.38-0.53), MAKE (HR, 0.72; 95% CI, 0.60-0.89), and MALO (HR, 0.61; 95% CI, 0.53-0.69). In contrast, compared to GLP-1RA monotherapy, combination therapy did not confer additional benefit except for all-cause mortality. Overall, combination therapy with GLP-1RA plus SGLT2i was associated with better clinical outcomes of MASLD, compared to SGLT2i monotherapy.
对于代谢功能障碍相关脂肪性肝病（MASLD），在钠-葡萄糖协同转运蛋白2抑制剂（SGLT2i）基础上加用胰高血糖素样肽-1受体激动剂（GLP-1RA）的影响尚不清楚。这项回顾性研究比较了GLP-1RA联合SGLT2i与单独使用SGLT2i治疗MASLD的效果。联合治疗与全因住院、全因死亡、主要不良心血管事件（MACE）、主要不良肾脏事件（MAKE）和主要不良肝脏结局（MALO）等主要复合结局的较低风险相关（风险比[HR]，0.87；95%置信区间[CI]，0.84-0.91）。联合治疗在全因住院（HR，0.86；95%CI，0.82-0.90）、全因死亡（HR，0.45；95%CI，0.38-0.53）、MAKE（HR，0.72；95%CI，0.60-0.89）和MALO（HR，0.61；95%CI，0.53-0.69）方面也显示出较低风险。相比之下，与GLP-1RA单药治疗相比，联合治疗除全因死亡外未带来额外益处。总体而言，与SGLT2i单药治疗相比，GLP-1RA联合SGLT2i的联合治疗与MASLD更好的临床结局相关。
