Association of GLP1-Receptor Agonists with Risk of Hepatocellular Carcinoma: A Retrospective Cohort Study.

IF 4 2区 医学 Q1 PHARMACOLOGY & PHARMACY
Joane Titus, Vinay Katukuri, Moheb Boktor, Ishak A Mansi
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引用次数: 0

Abstract

Background: The use of glucagon-like peptide-1 receptor agonists (GLP-1RA) has exponentially increased owing to their favorable cardio-renal-metabolic effects. Some studies have raised concerns about a potential association between GLP-1RA use and malignancy. This study aimed to examine the association between GLP-1RA use and risk of hepatocellular carcinoma (HCC).

Methods: This retrospective propensity score (PS)-matched cohort study used data from the Veterans Health Administration (years 2006-2021). Using a new-user active comparator design, the study included adults who initiated a GLP-1RA or dipeptidyl peptidase-4 inhibitor (DPP4i) as an active comparator and had no prior history of HCC or liver transplantation. The primary outcome was incident HCC. We developed a PS that included 133 variables encompassing diabetes severity, hepatic conditions, liver disease scores, vital signs, laboratory investigations, comorbidity scores, and use of other medication classes.

Results: Of 147,969 GLP-1RA and 263,664 DPP4i users, 100,248 pairs of GLP-1RA and DPP4i users were PS-matched. Hepatocellular carcinoma occurred in 302 (0.30%) GLP-1RA users and in 230 (0.23%) DPP4i users (odds ratio [OR]: 1.31, 95% confidence interval [95% CI]: 1.11-1.56). Secondary analysis, which stratified patients by duration of medication use, showed an increased risk of HCC in association with GLP-1RA use > 6 months, but similar HCC risk if medication use was < 6 months (OR: 0.96; 95% CI 0.68-1.35).

Conclusions: Glucagon-like peptide-1 receptor agonists use was associated with a modest but statistically significant increase in HCC risk versus DPP4i use. Although the reported benefits of GLP-1RA seem to far exceed this modest increased risk, further studies are warranted due to exponentially increasing GLP-1RA use and their broadening indications.

glp1受体激动剂与肝细胞癌风险的关联:一项回顾性队列研究
背景:胰高血糖素样肽-1受体激动剂(GLP-1RA)由于其良好的心肾代谢作用,其使用呈指数增长。一些研究对GLP-1RA的使用与恶性肿瘤之间的潜在关联提出了担忧。本研究旨在探讨GLP-1RA的使用与肝细胞癌(HCC)风险之间的关系。方法:这项回顾性倾向评分(PS)匹配的队列研究使用了退伍军人健康管理局(2006-2021年)的数据。该研究采用新用户活性比较物设计,纳入了开始GLP-1RA或二肽基肽酶-4抑制剂(DPP4i)作为活性比较物的成年人,并且没有HCC或肝移植史。主要终点是HCC的发生率。我们制定了一个包括糖尿病严重程度、肝脏状况、肝脏疾病评分、生命体征、实验室调查、合并症评分和其他药物类别使用等133个变量的PS。结果:在147,969名GLP-1RA和263,664名DPP4i使用者中,100,248对GLP-1RA和DPP4i使用者是ps匹配的。302例(0.30%)GLP-1RA使用者发生肝细胞癌,230例(0.23%)DPP4i使用者发生肝细胞癌(优势比[OR]: 1.31, 95%可信区间[95% CI]: 1.11-1.56)。根据用药时间对患者进行分层的二次分析显示,GLP-1RA用药6个月以上的患者发生HCC的风险增加,但用药< 6个月的患者发生HCC的风险相似(OR: 0.96;95% ci 0.68-1.35)。结论:与使用DPP4i相比,使用胰高血糖素样肽-1受体激动剂与HCC风险适度但有统计学意义的增加相关。尽管报道的GLP-1RA的益处似乎远远超过了这种适度增加的风险,但由于GLP-1RA的使用呈指数增长及其适应症的扩大,进一步的研究是有必要的。
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来源期刊
Drug Safety
Drug Safety 医学-毒理学
CiteScore
7.60
自引率
7.10%
发文量
112
审稿时长
6-12 weeks
期刊介绍: Drug Safety is the official journal of the International Society of Pharmacovigilance. The journal includes: Overviews of contentious or emerging issues. Comprehensive narrative reviews that provide an authoritative source of information on epidemiology, clinical features, prevention and management of adverse effects of individual drugs and drug classes. In-depth benefit-risk assessment of adverse effect and efficacy data for a drug in a defined therapeutic area. Systematic reviews (with or without meta-analyses) that collate empirical evidence to answer a specific research question, using explicit, systematic methods as outlined by the PRISMA statement. Original research articles reporting the results of well-designed studies in disciplines such as pharmacoepidemiology, pharmacovigilance, pharmacology and toxicology, and pharmacogenomics. Editorials and commentaries on topical issues. Additional digital features (including animated abstracts, video abstracts, slide decks, audio slides, instructional videos, infographics, podcasts and animations) can be published with articles; these are designed to increase the visibility, readership and educational value of the journal’s content. In addition, articles published in Drug Safety Drugs may be accompanied by plain language summaries to assist readers who have some knowledge of, but not in-depth expertise in, the area to understand important medical advances.
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