Tsuriya Daisuke, Kobayashi Kazuo, Takeshita Kei, Hashimoto Takuya, Kimura Moritsugu, Muta Yoshimi, Yokomizo Hisashi, Takashi Yuichi, Tsukamoto Shunichiro, Tamura Kouichi, Kanasaki Keizo, Kawanami Daiji, Toyoda Masao
Division of Endocrinology and Metabolism, 2nd Department of Internal Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan.
Department of Medical Science and Cardiorenal Medicine, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
J Diabetes Investig. 2025 Jul;16(7):1243-1253. doi: 10.1111/jdi.70066. Epub 2025 May 7.
The favor effect on liver disease by odium-glucose cotransporter inhibitor (SGLT2i) and GLP-1 receptor agonist (GLP1Ra) was reported; however, the effect of the combination treatment of these drugs was not well known.
We retrospectively analyzed data for 643 patients with type 2 diabetes receiving SGLT2i + GLP1Ra combination treatment for at least 1 year (331 and 312 patients in the GLP1Ra- and SGLT2i-preceding groups, respectively). Propensity score (PS) matching was used to compare the effects of the preceding drugs on liver function.
The mean AST and ALT values at baseline, at the initiation of combination treatment, and at final observation were 29.8 ± 20.0 and 37.7 ± 29.5, 28.7 ± 17.3 and 35.3 ± 6.0, 26.0 ± 14.6 and 30.1 ± 21.6 IU/L, respectively, indicative of significant improvements in liver function (P < 0.001). Conversely, significant progress in the fibrosis-4 (FIB-4) index category was observed even after the combination treatment (P = 0.03). Subgroup analysis revealed that a significant decrease in ALT was observed only in patients with a baseline ALT ≥30 IU/L after the combination treatment (P = 0.005). Improvement of the FIB-4 index category was observed in patients in the baseline FIB-4 index ≥2.6 group and in the 1.3 ≤FIB-4 index <2.6 group (46% and 19%, respectively). The matched model showed no significant differences in liver function after combination treatment between the SGLT2i- and GLP1Ra-preceding groups.
SGLT2i + GLP1Ra combination treatment significantly improved liver dysfunction and prevented the progression of FIB-4 index category among patients with an FIB-4 index ≥1.3.
已有报道称钠-葡萄糖协同转运蛋白抑制剂(SGLT2i)和胰高血糖素样肽-1受体激动剂(GLP1Ra)对肝脏疾病有有益作用;然而,这两种药物联合治疗的效果尚不清楚。
我们回顾性分析了643例接受SGLT2i + GLP1Ra联合治疗至少1年的2型糖尿病患者的数据(GLP1Ra先行组和SGLT2i先行组分别有331例和312例患者)。采用倾向评分(PS)匹配法比较先行药物对肝功能的影响。
基线时、联合治疗开始时和最终观察时的平均谷草转氨酶(AST)和谷丙转氨酶(ALT)值分别为29.8±20.0和37.7±29.5、28.7±17.3和35.3±6.0、26.0±14.6和30.1±21.6 IU/L,表明肝功能有显著改善(P < 0.001)。相反,即使在联合治疗后,纤维化-4(FIB-4)指数类别仍有显著进展(P = 0.03)。亚组分析显示,联合治疗后仅基线ALT≥30 IU/L的患者ALT显著下降(P = 0.005)。在基线FIB-4指数≥2.6组和1.3≤FIB-4指数<2.6组的患者中观察到FIB-4指数类别有所改善(分别为46%和19%)。匹配模型显示,SGLT2i先行组和GLP1Ra先行组在联合治疗后的肝功能无显著差异。
SGLT2i + GLP1Ra联合治疗可显著改善肝功能不全,并预防FIB-4指数≥1.3的患者中FIB-4指数类别的进展。