Effect of ipragliflozin on liver enzymes in type 2 diabetes mellitus: a meta-analysis of randomized controlled trials

Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) is estimated to affect upto 70–80% of people with type 2 diabetes mellitus (T2DM). Although several anti-hyperglycemic drugs have been shown to be effective in such patients, there remains an unmet need for newer drugs. The objective of this meta-analysis was to analyze the effect of ipragliflozin on aspartate aminotransferase (AST), alanine transaminase (ALT), and gamma-glutamyl transpeptidase (GGT) levels in patients with T2DM. A literature search on electronic databases was conducted to identify potential randomized clinical trials (RCT) as per predetermined study selection criteria. Mean difference (MD) was calculated using Cochrane review manager. Twelve studies were included in the meta-analysis, including 1349 subjects. Compared to the control group, ipragliflozin as a monotherapy showed a significant reduction in levels of ALT at week 12 (<i>p</i> = 0.02) and at week 24 (<i>p</i> = 0.007), GGT at week 12 (<i>p</i> &lt; 0.00001). Ipragliflozin as an add-on therapy showed significant reduction in levels of AST at week 24 (<i>p</i> &lt; 0.00001), ALT at week 12 (<i>p</i> = 0.002), ALT at week 24 (<i>p</i> &lt; 0.00001), and GGT at week 24 (<i>p</i> &lt; 0.00001). Findings suggest the beneficial effects of ipragliflozin on liver enzymes. Further large-scale RCTs are required to confirm ipragliflozin’s role for liver-related conditions in T2DM.

据估算，代谢功能障碍相关性脂肪性肝病（Metabolic Dysfunction-Associated Steatotic Liver Disease, MASLD）在2型糖尿病（type 2 diabetes mellitus, T2DM）患者中的罹患率可达70%~80%。尽管已有多种降糖药物被证实可有效应用于此类患者，但目前仍存在新型药物的未被满足的临床需求。本荟萃分析的目的为探讨艾格列净（ipragliflozin）对2型糖尿病患者天门冬氨酸氨基转移酶（aspartate aminotransferase, AST）、丙氨酸氨基转移酶（alanine transaminase, ALT）及γ-谷氨酰转移酶（gamma-glutamyl transpeptidase, GGT）水平的影响。研究人员通过电子数据库开展文献检索，按照预先设定的研究纳入标准筛选潜在的随机对照试验（randomized clinical trials, RCT）。采用Cochrane系统评价管理器计算均数差（Mean difference, MD）。本荟萃分析共纳入12项研究，合计1349名受试者。与对照组相比，艾格列净单药治疗可在第12周（p=0.02）及第24周（p=0.007）显著降低ALT水平，在第12周显著降低GGT水平（p<0.00001）。艾格列净作为附加治疗方案时，可在第24周显著降低AST水平（p<0.00001）、第12周显著降低ALT水平（p=0.002）、第24周显著降低ALT水平（p<0.00001），并于第24周显著降低GGT水平（p<0.00001）。研究结果提示，艾格列净对肝脏酶学指标具有有益作用。未来仍需开展大规模随机对照试验，以明确艾格列净在2型糖尿病患者肝脏相关疾病中的应用价值。