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二肽基肽酶-4 抑制剂可能会加速糖尿病合并肝硬化患者的肝硬化失代偿:一项来自中国台湾的全国基于人群的队列研究。

Dipeptidyl peptidase-4 inhibitors may accelerate cirrhosis decompensation in patients with diabetes and liver cirrhosis: a nationwide population-based cohort study in Taiwan.

机构信息

Dr. Yen's Clinic, No. 15, Shanying Road, Gueishan District, Taoyuan, 33354, Taiwan.

Division of Allergy, Immunology and Rheumatology Chung, Shan Medical University Hospital, No. 110, Sec. 1, Jianguo N. Rd., South District, Taichung City, 40201, Taiwan.

出版信息

Hepatol Int. 2021 Feb;15(1):179-190. doi: 10.1007/s12072-020-10122-1. Epub 2021 Jan 10.

DOI:10.1007/s12072-020-10122-1
PMID:33423239
Abstract

BACKGROUND/PURPOSE: Management of type 2 diabetes mellitus (T2DM) in patients with liver cirrhosis is complex and suboptimal, but no clinical trial has adequately investigated antidiabetic drug use for such patients. We evaluate the risk of mortality, cardiovascular events, and hepatic outcomes between dipeptidyl peptidase-4 (DPP-4) inhibitor users and nonusers in patients with type 2 diabetes mellitus (T2DM) and cirrhosis.

METHODS

We selected 2828 paired propensity score matched DPP-4 inhibitor users and nonusers from a cohort of T2DM with compensated liver cirrhosis between January 1, 2007, and December 31, 2012. Cox proportional hazards models were used to assess the risk of main outcomes for DPP-4 inhibitor users.

RESULTS

The incidence rate of decompensated cirrhosis during follow-up was 2.20 and 1.53 per 100 patient-years (adjusted hazard ratio [aHR] 1.35, 95% confidence interval [CI] 1.03-1.77) for DPP-4 inhibitor users and nonusers, respectively. The aHRs (95% CI) of variceal bleeding and hepatic failure were 1.67 (1.11-2.52) and 1.35 (1.02-1.79), respectively, for DPP-4 inhibitor users over nonusers. The risk of all-cause mortality, hepatocellular carcinoma, and major cardiovascular events between DPP-4 inhibitor users and nonusers were not statistically different.

CONCLUSIONS

This study found that DPP-4 inhibitor users were associated with higher risks of decompensated cirrhosis and hepatic failure than did nonusers among patients with T2DM and compensated liver cirrhosis. We must continue to search for appropriate antidiabetic drugs for patients with liver cirrhosis.

摘要

背景/目的:2 型糖尿病(T2DM)合并肝硬化患者的糖尿病管理较为复杂,且并不完善,但目前尚无临床试验充分评估此类患者的降糖药物使用情况。我们评估了 2 型糖尿病(T2DM)合并肝硬化患者使用二肽基肽酶-4(DPP-4)抑制剂与未使用者之间的死亡率、心血管事件和肝脏结局风险。

方法

我们从 2007 年 1 月 1 日至 2012 年 12 月 31 日期间的 T2DM 代偿性肝硬化队列中选择了 2828 对 DPP-4 抑制剂使用者和非使用者进行配对倾向评分匹配。使用 Cox 比例风险模型评估 DPP-4 抑制剂使用者的主要结局风险。

结果

在随访期间,失代偿性肝硬化的发生率分别为 DPP-4 抑制剂使用者和非使用者每 100 患者年 2.20 和 1.53 例(调整后的危险比[aHR]1.35,95%置信区间[CI]1.03-1.77)。DPP-4 抑制剂使用者发生静脉曲张出血和肝功能衰竭的 aHR(95%CI)分别为 1.67(1.11-2.52)和 1.35(1.02-1.79)。DPP-4 抑制剂使用者与非使用者之间的全因死亡率、肝细胞癌和主要心血管事件风险无统计学差异。

结论

本研究发现,与非使用者相比,T2DM 合并代偿性肝硬化患者使用 DPP-4 抑制剂与失代偿性肝硬化和肝功能衰竭风险增加相关。我们必须继续为肝硬化患者寻找合适的降糖药物。

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