Colosimo Santo, Ravaioli Federico, Petroni Maria L, Brodosi Lucia, Marchignoli Francesca, Barbanti Francesca A, Sasdelli Anna S, Marchesini Giulio, Pironi Loris
Department of Medical and Surgical Sciences, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy.
Fondazione IRCSS Ca' Granda, Ospedale Maggiore Policlinico di Milano, Milan, Italy.
Liver Int. 2021 Apr;41(4):731-742. doi: 10.1111/liv.14799. Epub 2021 Feb 10.
BACKGROUND & AIMS: There is intense research for drugs able to reduce disease progression in nonalcoholic fatty liver disease. We aimed to test the impact of novel antidiabetic drugs (dipeptidyl-peptidase-4 inhibitors - DPP-4Is, glucagon-like peptide-1 receptor agonists - GLP-1RAs, sodium-glucose cotransporter-2 inhibitors - SGLT-2Is) on non-invasive biomarkers of steatosis (fatty liver index, FLI) and fibrosis (Fibrosis-4 score, FIB-4) in patients with type 2 diabetes (T2D).
Clinical, anthropometric and biochemical parameters were retrospectively analysed in 637 consecutive T2D patients switched from metformin w/wo sulfonylureas and/or pioglitazone to DPP-4Is, GLP-1RAs and SGLT-2Is in a tertiary care setting. 165 patients maintained on original treatments served as controls. The effects on FLI and FIB-4 at 6- and 12-month follow-up were analysed by logistic regression after adjustment for baseline differences, computed by propensity scores, and additional adjustment for changes in glycosylated hemoglobin (HbA1c) and body mass index.
Body mass index, HbA1c and aminotrasferases significantly decreased following switching to GLP-1RAs and SGLT2-Is, compared with both controls and DPP-4Is, whereas only HbA1c was reduced on DPP-4Is. FLI and FIB-4 were reduced on GLP-1RA and SGLT-2I; logistic regression analysis confirmed a significant improvement of both biomarkers after adjustment for propensity score. The shift of FIB-4 values towards the category ruling out advanced fibrosis was maintained after additional adjustment for confounders. These effects were confirmed in a sensitivity analysis on effect size.
Glucagon-like peptide-1 receptor agonists and SGLT-2Is improve biomarkers of steatosis and fibrosis, in keeping with beneficial effects on liver disease progression, and should be considered the treatment of choice in T2D.
针对能够减缓非酒精性脂肪性肝病疾病进展的药物，正在进行深入研究。我们旨在测试新型抗糖尿病药物（二肽基肽酶-4抑制剂 - DPP-4Is、胰高血糖素样肽-1受体激动剂 - GLP-1RAs、钠-葡萄糖协同转运蛋白-2抑制剂 - SGLT-2Is）对2型糖尿病（T2D）患者脂肪变性（脂肪肝指数，FLI）和纤维化（纤维化-4评分，FIB-4）的非侵入性生物标志物的影响。
在三级医疗环境中，对637例从二甲双胍加/不加磺脲类药物和/或吡格列酮转换为DPP-4Is、GLP-1RAs和SGLT-2Is的连续性T2D患者的临床、人体测量和生化参数进行回顾性分析。165例维持原治疗的患者作为对照。在根据倾向得分调整基线差异后，通过逻辑回归分析6个月和12个月随访时对FLI和FIB-4的影响，并对糖化血红蛋白（HbA1c）和体重指数的变化进行额外调整。
与对照组和DPP-4Is相比，转换为GLP-1RAs和SGLT-2Is后，体重指数、HbA1c和转氨酶显著降低，而DPP-4Is仅降低了HbA1c。GLP-1RA和SGLT-2I降低了FLI和FIB-4；逻辑回归分析证实，在调整倾向得分后，这两种生物标志物均有显著改善。在对混杂因素进行额外调整后，FIB-4值向排除晚期纤维化类别的转变得以维持。这些效应在效应量的敏感性分析中得到证实。
胰高血糖素样肽-1受体激动剂和SGLT-2Is改善了脂肪变性和纤维化的生物标志物，与对肝病进展的有益作用一致，应被视为T2D的首选治疗方法。
