Division of Gastroenterology and Hepatology, Department of Internal Medicine, Seoul National University College of Medicine, Seoul Metropolitan Government Boramae Medical Center, Seoul, Republic of Korea.
Department of Public Health Sciences, Graduate School of Public Health, Seoul National University, Seoul, Republic of Korea.
JAMA Intern Med. 2024 Apr 1;184(4):375-383. doi: 10.1001/jamainternmed.2023.8029.
Several oral antidiabetic drug (OAD) classes can potentially improve patient outcomes in nonalcoholic fatty liver disease (NAFLD) to varying degrees, but clinical data on which class is favored are lacking.
To investigate which OAD is associated with the best patient outcomes in NAFLD and type 2 diabetes (T2D).
DESIGN, SETTING, AND PARTICIPANTS: This retrospective nonrandomized interventional cohort study used the National Health Information Database, which provided population-level data for Korea. This study involved patients with T2D and concomitant NAFLD.
Receiving either sodium-glucose cotransporter 2 (SGLT2) inhibitors, thiazolidinediones, dipeptidyl peptidase-4 (DPP-4) inhibitors, or sulfonylureas, each combined with metformin for 80% or more of 90 consecutive days.
The main outcomes were NAFLD regression assessed by the fatty liver index and composite liver-related outcome (defined as liver-related hospitalization, liver-related mortality, liver transplant, and hepatocellular carcinoma) using the Fine-Gray model regarding competing risks.
In total, 80 178 patients (mean [SD] age, 58.5 [11.9] years; 43 007 [53.6%] male) were followed up for 219 941 person-years, with 4102 patients experiencing NAFLD regression. When compared with sulfonylureas, SGLT2 inhibitors (adjusted subdistribution hazard ratio [ASHR], 1.99 [95% CI, 1.75-2.27]), thiazolidinediones (ASHR, 1.70 [95% CI, 1.41-2.05]), and DPP-4 inhibitors (ASHR, 1.45 [95% CI, 1.31-1.59]) were associated with NAFLD regression. SGLT2 inhibitors were associated with a higher likelihood of NAFLD regression when compared with thiazolidinediones (ASHR, 1.40 [95% CI, 1.12-1.75]) and DPP-4 inhibitors (ASHR, 1.45 [95% CI, 1.30-1.62]). Only SGLT2 inhibitors (ASHR, 0.37 [95% CI, 0.17-0.82]), not thiazolidinediones or DPP-4 inhibitors, were significantly associated with lower incidence rates of adverse liver-related outcomes when compared with sulfonylureas.
The results of this cohort study suggest that physicians may lean towards prescribing SGLT2 inhibitors as the preferred OAD for individuals with NAFLD and T2D, considering their potential benefits in NAFLD regression and lower incidences of adverse liver-related outcomes. This observational study should prompt future research to determine whether prescribing practices might merit reexamination.
几种口服抗糖尿病药物（OAD）类药物在不同程度上可能改善非酒精性脂肪性肝病（NAFLD）患者的预后，但缺乏关于哪种药物类别的临床数据。
研究哪种 OAD 与 NAFLD 和 2 型糖尿病（T2D）患者的最佳预后相关。
设计、地点和参与者：这是一项回顾性非随机干预性队列研究，使用了提供韩国人群水平数据的国家健康信息数据库。本研究涉及同时患有 T2D 和 NAFLD 的患者。
接受钠-葡萄糖共转运蛋白 2（SGLT2）抑制剂、噻唑烷二酮类、二肽基肽酶-4（DPP-4）抑制剂或磺酰脲类药物中的任何一种，每种药物与二甲双胍联合使用，连续 90 天的比例达到 80%或以上。
主要结局是使用 Fine-Gray 模型评估的通过脂肪肝指数和复合肝脏相关结局（定义为肝脏相关住院、肝脏相关死亡率、肝移植和肝细胞癌）评估的 NAFLD 缓解情况，该模型涉及竞争风险。
共有 80178 名患者（平均[标准差]年龄，58.5[11.9]岁；43007[53.6%]为男性）接受了 219941 人年的随访，其中 4102 名患者出现了 NAFLD 缓解。与磺酰脲类药物相比，SGLT2 抑制剂（调整后的亚分布风险比[ASHR]，1.99[95%置信区间，1.75-2.27]）、噻唑烷二酮类（ASHR，1.70[95%置信区间，1.41-2.05]）和 DPP-4 抑制剂（ASHR，1.45[95%置信区间，1.31-1.59]）与 NAFLD 缓解相关。与噻唑烷二酮类药物（ASHR，1.40[95%置信区间，1.12-1.75]）和 DPP-4 抑制剂（ASHR，1.45[95%置信区间，1.30-1.62]）相比，SGLT2 抑制剂与 NAFLD 缓解的可能性更高。只有 SGLT2 抑制剂（ASHR，0.37[95%置信区间，0.17-0.82]），而不是噻唑烷二酮类药物或 DPP-4 抑制剂，与磺酰脲类药物相比，与较低的不良肝脏相关结局发生率显著相关。
这项队列研究的结果表明，考虑到 SGLT2 抑制剂在 NAFLD 缓解和不良肝脏相关结局发生率较低方面的潜在益处，医生可能倾向于将其作为治疗 NAFLD 和 T2D 患者的首选 OAD。这项观察性研究应促使未来开展研究，以确定处方实践是否值得重新评估。
