Krishnan Arunkumar, Schneider Carolin V, Hadi Yousaf, Mukherjee Diptasree, AlShehri Bandar, Alqahtani Saleh A
Department of Supportive Oncology, Levine Cancer Institute, Atrium Health, Charlotte, NC, USA.
Division of Gastroenterology and Hepatology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Diabetologia. 2024 Mar;67(3):483-493. doi: 10.1007/s00125-023-06057-5. Epub 2023 Dec 20.
AIMS/HYPOTHESIS: We aimed to determine whether the use of glucagon-like peptide-1 receptor agonists (GLP-1RA) in individuals with non-alcoholic fatty liver disease (NAFLD) and type 2 diabetes mellitus decreases the risk of new-onset adverse cardiovascular events (CVEs) and mortality rate compared with other glucose-lowering drugs in a real setting at a population level.
We conducted a population-based propensity-matched retrospective cohort study using TriNetX. The cohort comprised patients over 20 years old who were newly treated with glucose-lowering drugs between 1 January 2013 and 31 December 2021, and followed until 30 September 2022. New users of GLP-1RAs were matched based on age, demographics, comorbidities and medication use by using 1:1 propensity matching with other glucose-lowering drugs. The primary outcome was the new onset of adverse CVEs, including heart failure, composite incidence of major adverse cardiovascular events (MACE; defined as unstable angina, myocardial infarction, or coronary artery procedures or surgeries) and composite cerebrovascular events (defined as the first occurrence of stroke, transient ischaemic attack, cerebral infarction, carotid intervention or surgery), and the secondary outcome was all-cause mortality. Cox proportional hazards models were used to estimate HRs.
The study involved 2,835,398 patients with both NAFLD and type 2 diabetes. When compared with the sodium-glucose cotransporter 2 (SGLT2) inhibitors group, the GLP-1RAs group showed no evidence of a difference in terms of new-onset heart failure (HR 0.97; 95% CI 0.93, 1.01), MACE (HR 0.95; 95% CI 0.90, 1.01) and cerebrovascular events (HR 0.99; 95% CI 0.94, 1.03). Furthermore, the two groups had no evidence of a difference in mortality rate (HR 1.06; 95% CI 0.97, 1.15). Similar results were observed across sensitivity analyses. Compared with other second- or third-line glucose-lowering medications, the GLP-1RAs demonstrated a lower rate of adverse CVEs, including heart failure (HR 0.88; 95% CI 0.85, 0.92), MACE (HR 0.89; 95% CI 0.85, 0.94), cerebrovascular events (HR 0.93; 95% CI 0.89, 0.96) and all-cause mortality rate (HR 0.70; 95% CI 0.66, 0.75).
CONCLUSIONS/INTERPRETATION: In individuals with NAFLD and type 2 diabetes, GLP-1RAs are associated with lower incidences of adverse CVEs and all-cause mortality compared with metformin or other second- and third-line glucose-lowering medications. However, there was no significant difference in adverse CVEs or all-cause mortality when compared with those taking SGLT2 inhibitors.
目的/假设：我们旨在确定在非酒精性脂肪性肝病（NAFLD）合并2型糖尿病的个体中，与其他降糖药物相比，使用胰高血糖素样肽-1受体激动剂（GLP-1RA）在人群水平的实际情况下是否会降低新发不良心血管事件（CVE）的风险和死亡率。
我们使用TriNetX进行了一项基于人群的倾向匹配回顾性队列研究。该队列包括2013年1月1日至2021年12月31日期间新接受降糖药物治疗的20岁以上患者，并随访至2022年9月30日。通过使用1:1倾向匹配与其他降糖药物，根据年龄、人口统计学、合并症和药物使用情况对GLP-1RA的新使用者进行匹配。主要结局是不良CVE的新发，包括心力衰竭、主要不良心血管事件（MACE；定义为不稳定型心绞痛、心肌梗死或冠状动脉手术或操作）的综合发生率和脑血管事件（定义为首次发生中风、短暂性脑缺血发作、脑梗死、颈动脉干预或手术），次要结局是全因死亡率。使用Cox比例风险模型估计风险比（HR）。
该研究纳入了2835398例NAFLD合并2型糖尿病患者。与钠-葡萄糖协同转运蛋白2（SGLT2）抑制剂组相比，GLP-1RA组在新发心力衰竭（HR 0.97；95%置信区间0.93，1.01）、MACE（HR 0.95；95%置信区间0.90，1.01）和脑血管事件（HR 0.99；95%置信区间0.94，1.03）方面没有差异证据。此外，两组在死亡率方面也没有差异证据（HR 1.06；95%置信区间0.97，1.15）。在敏感性分析中观察到了类似结果。与其他二线或三线降糖药物相比，GLP-1RA显示出较低的不良CVE发生率，包括心力衰竭（HR 0.88；95%置信区间0.85，0.92）、MACE（HR 0.89；95%置信区间0.85，0.94）、脑血管事件（HR 0.93；95%置信区间0.89，0.96）和全因死亡率（HR 0.70；95%置信区间0.66，0.75）。
结论/解读：在NAFLD合并2型糖尿病的个体中，与二甲双胍或其他二线和三线降糖药物相比，GLP-1RA与较低的不良CVE发生率和全因死亡率相关。然而，与服用SGLT2抑制剂的患者相比，不良CVE或全因死亡率没有显著差异。
