Ma Gang, Zhang Song, Yu Baozhong
Department of hepatobiliary surgery, The First People's Hospital of Guangyuan, Guangyuan, Sichuan, China.
Departmant of Pharmacy, The First People's Hospital of Guangyuan, Guangyuan, Sichuan, China.
Curr Ther Res Clin Exp. 2024 Dec 4;102:100768. doi: 10.1016/j.curtheres.2024.100768. eCollection 2025.
Type 2 diabetes mellitus (T2DM) and nonalcoholic fatty liver disease (NAFLD) are highly prevalent diseases that constitute enormous public health problems. The efficacy of dipeptidyl peptidase-4 (DPP-4) inhibitors in blood glucose control in T2DM patients with NAFLD has been established, but little is known about its effect on liver enzyme levels.
This meta-analysis aimed to evaluate the influences of DPP-4 inhibitors on alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in patients with T2DM and NAFLD.
To identify the relevant studies, we searched PubMed, Embase, the Cochrane Library, Wanfang Data, and China National Knowledge Infrastructure. Means differences in liver enzymes and metabolic outcomes were meta-analyzed using a random-effects model, with subgroup analyses by gender, age, area, follow-up duration, and type of DPP-4 inhibitor. Quality assessment of the included studies was conducted using the revised Cochrane risk of bias tool.
A total of 1323 patients from 16 studies were included in this meta-analysis. The results of analysis of DPP-4 inhibitors showed that the mean difference was -6.19 (95% confidence interval [CI]: -9.45 to -2.92) for ALT and -5.17 (95% CI: -8.10 to -2.23) for AST; this effect was statistically significant from the placebo group which indicates the beneficial effect on liver enzymes. Subgroup analysis revealed that while there were no significant gender differences in enzyme reductions, individuals over 55 years old experienced more pronounced decreases in ALT. Notably, Asian studies showed significant reductions in liver enzymes, contrasting with the minor variations observed in Euramerican regions, and the effectiveness of DPP-4 inhibitors was particularly pronounced during shorter follow-up periods, with effects diminishing over time. Regarding secondary outcomes, there was a notable improvement in gamma-glutamyl transpeptidase, with a mean reduction, and in HbA1c levels, indicating improved glycemic control. Homeostatic model assessment for insulin resistance levels also improved, reflecting better insulin sensitivity. Additionally, adverse event analysis confirmed that DPP-4 inhibitors were well-tolerated with a favorable safety profile.
DPP-4 inhibitors appear to enhance glycemic control and improve liver enzyme levels, suggesting a potentially effective therapeutic approach for managing T2DM/NAFLD and highlighting their broader metabolic benefits.
2型糖尿病（T2DM）和非酒精性脂肪性肝病（NAFLD）是高度流行的疾病，构成了巨大的公共卫生问题。二肽基肽酶-4（DPP-4）抑制剂在合并NAFLD的T2DM患者血糖控制中的疗效已得到证实，但对其对肝酶水平的影响知之甚少。
本荟萃分析旨在评估DPP-4抑制剂对合并NAFLD的T2DM患者丙氨酸氨基转移酶（ALT）和天冬氨酸氨基转移酶（AST）的影响。
为了确定相关研究，我们检索了PubMed、Embase、Cochrane图书馆、万方数据和中国知网。使用随机效应模型对肝酶和代谢指标的均值差异进行荟萃分析，并按性别、年龄、地区、随访时间和DPP-4抑制剂类型进行亚组分析。使用修订的Cochrane偏倚风险工具对纳入研究进行质量评估。
本荟萃分析共纳入了16项研究中的1323例患者。DPP-4抑制剂的分析结果显示，ALT的平均差异为-6.19（95%置信区间[CI]：-9.45至-2.92），AST的平均差异为-5.17（95%CI：-8.10至-2.23）；与安慰剂组相比，这一效应具有统计学意义，表明对肝酶有有益作用。亚组分析显示，虽然酶降低方面没有显著的性别差异，但55岁以上的个体ALT下降更为明显。值得注意的是，亚洲的研究显示肝酶有显著降低，这与欧美地区观察到的微小变化形成对比，并且DPP-4抑制剂在较短的随访期内效果尤为明显，随着时间的推移效果逐渐减弱。关于次要结局，γ-谷氨酰转肽酶有显著改善，均值降低，糖化血红蛋白（HbA1c）水平也有所改善，表明血糖控制得到改善。胰岛素抵抗水平的稳态模型评估也有所改善，反映出胰岛素敏感性更好。此外，不良事件分析证实DPP-4抑制剂耐受性良好，安全性良好。
DPP-4抑制剂似乎能增强血糖控制并改善肝酶水平，提示其可能是治疗T2DM/NAFLD的有效治疗方法，并突出了其更广泛的代谢益处。
