Research Center for Immunodeficiencies, Pediatrics Center of Excellence, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran.
Non-Communicable Diseases Research Center, Endocrinology and Metabolism Population Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran.
Diabet Med. 2024 Nov;41(11):e15437. doi: 10.1111/dme.15437. Epub 2024 Sep 28.
While randomized controlled trials data on the long-term effect of glucose-lowering drugs (GLDs) on liver-related outcomes are lacking, population-based studies have evaluated the associations of GLDs with liver-related outcomes in individuals with type 2 diabetes (T2D). we aimed to conduct a systematic review of population-based studies evaluating the effects of GLDs on liver-related outcomes in people with T2D.
PubMed, Web of Science, and Embase databases were systematically searched for population-based studies testing the associations of GLDs with liver-related outcomes in individuals with T2D and no liver disease other than non-alcoholic fatty liver disease (NAFLD) from inception to 23 February 2024. GLDs included SGLT2is, TZDs, insulin, GLP-1 RAs and dipeptidyl peptidase-4 inhibitors (DPP4Is).
Ten cohort studies, comprising 1,274,641 participants, met the inclusion criteria. The median follow-up period ranged from 8.9 to 76 months. Of all the GLDs under investigation, SGLT2is were associated with the strongest reduction in NAFLD incidence, cirrhosis, and composite liver-related events compared to other medications. TZDs were associated with a reduced risk of developing NAFLD and cirrhosis but were not significantly associated with a lower incidence of hepatocellular carcinoma. GLP-1 RAs demonstrated a significant association with reduced liver-related mortality.
Observational data from population-based studies suggest that GLDs such as SGLT2is are associated with beneficial long-term liver-related outcomes in T2D patients with NAFLD. Additional studies, including randomized controlled trials with long-term follow-up, are needed to confirm these findings.
PROSPERO CRD442024536872.
虽然缺乏关于降糖药物（GLD）对肝脏相关结局长期影响的随机对照试验数据，但基于人群的研究已经评估了 GLD 与 2 型糖尿病（T2D）患者肝脏相关结局的相关性。我们旨在对评估 GLD 对无除非酒精性脂肪性肝病（NAFLD）以外的肝脏疾病的 T2D 患者肝脏相关结局影响的基于人群的研究进行系统综述。
从建库至 2024 年 2 月 23 日，我们系统地检索了 PubMed、Web of Science 和 Embase 数据库，以寻找评估 GLD 与无除非酒精性脂肪性肝病（NAFLD）以外的肝脏疾病的 T2D 患者肝脏相关结局相关性的基于人群的研究。GLD 包括 SGLT2is、TZDs、胰岛素、GLP-1 RAs 和二肽基肽酶-4 抑制剂（DPP4Is）。
符合纳入标准的共有 10 项队列研究，包含 1274641 名参与者。中位随访时间范围为 8.9 至 76 个月。在所研究的所有 GLD 中，与其他药物相比，SGLT2is 与 NAFLD 发生率、肝硬化和复合肝脏相关事件的最强降低相关。TZDs 与发生 NAFLD 和肝硬化的风险降低相关，但与肝细胞癌发生率降低无显著相关性。GLP-1 RAs 显示与降低肝脏相关死亡率显著相关。
基于人群的研究的观察性数据表明，SGLT2is 等 GLD 与 NAFLD 的 T2D 患者的有益的长期肝脏相关结局相关。需要包括长期随访的随机对照试验在内的进一步研究来证实这些发现。
PROSPERO CRD442024536872。
