OBJECTIVE To determine whether the use of dipeptidyl peptidase 4 (DPP-4) inhibitors and glucagon-like peptide 1 receptor agonists (GLP-1 RAs), separately, is associated with an increased risk of acute liver injury compared with the use of sodium–glucose cotransporter 2 (SGLT-2) inhibitors. RESEARCH DESIGN AND METHODS We used the U.K. Clinical Practice Research Datalink linked with the Hospital Episode Statistics Admitted Patient Care and the Office for National Statistics databases to assemble two new-user, active-comparator cohorts. The first included 106,310 initiators of DPP-4 inhibitors and 27,277 initiators of SGLT-2 inhibitors, while the second included 9,470 initiators of GLP-1 RAs and 26,936 initiators of SGLT-2 inhibitors. Cox proportional hazards models with propensity score fine stratification weighting were used to estimate hazard ratios (HRs) and 95% CIs of acute liver injury. RESULTS Compared with SGLT-2 inhibitors, DPP-4 inhibitors were associated with a 53% increased risk of acute liver injury (HR 1.53, 95% CI 1.02–2.30). In contrast, GLP-1 RAs were not associated with an overall increased risk of acute liver injury (HR 1.11, 95% CI 0.57–2.16). However, an increased risk was observed among female users of both DPP-4 inhibitors (HR 3.22, 95% CI 1.67–6.21) and GLP-1 RAs (HR 3.23, 95% CI 1.44–7.25). CONCLUSIONS In this population-based study, DPP-4 inhibitors were associated with an increased risk of acute liver injury compared with SGLT-2 inhibitors in patients with type 2 diabetes. In contrast, an increased risk of acute liver injury was observed only among female GLP-1 RA users.

中文翻译：

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以肠促胰岛素为基础的药物与 2 型糖尿病患者急性肝损伤的风险

目的 确定与使用钠相比，使用二肽基肽酶 4 (DPP-4) 抑制剂和胰高血糖素样肽 1 受体激动剂 (GLP-1 RAs) 是否会增加急性肝损伤的风险——葡萄糖协同转运蛋白 2 (SGLT-2) 抑制剂。研究设 第一个包括 106,310 个 DPP-4 抑制剂起始者和 27,277 个 SGLT-2 抑制剂起始者，而第二个包括 9,470 个 GLP-1 RA 起始者和 26,936 个 SGLT-2 抑制剂起始者。使用倾向评分精细分层加权的 Cox 比例风险模型来估计急性肝损伤的风险比 (HR) 和 95% CI。结果 与 SGLT-2 抑制剂相比，DPP-4 抑制剂与急性肝损伤风险增加 53% 相关（HR 1.53，95% CI 1.02–2.30）。相比之下，GLP-1 RA 与急性肝损伤的总体风险增加无关（HR 1.11, 95% CI 0.57–2.16）。然而，在 DPP-4 抑制剂 (HR 3.22, 95% CI 1.67–6.21) 和 GLP-1 RA (HR 3.23, 95% CI 1.44–7.25) 的女性使用者中观察到风险增加。结论 在这项基于人群的研究中，与 SGLT-2 抑制剂相比，在 2 型糖尿病患者中，DPP-4 抑制剂与急性肝损伤风险增加相关。相比之下，