Effectiveness of Metformin in Preventing Herpes Zoster Japanese Patients With Type 2 Diabetes: A Target Trial Emulation

IF 4.6 3区医学 Q1 VIROLOGY

Journal of Medical Virology Pub Date : 2025-09-14 DOI:10.1002/jmv.70606

Shunsuke Hiroki, Toshiki Fukasawa, Kasumi Yokogawa, Koji Kawakami

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Abstract

Patients with type 2 diabetes have a higher risk of herpes zoster (HZ). Although metformin may reduce this risk via immunomodulatory effects, prior evidence is limited by confounding by indication and an unclear causal estimand. We aimed to estimate the per-protocol effect of sustained metformin use on the risk of HZ in comparison with dipeptidyl peptidase-4 (DPP-4) inhibitors, for which no evidence suggests an elevated HZ risk. We emulated a target trial using a Japanese claims database (April 2012–December 2023) to assess the 4-year risk of HZ among new users of either metformin or a DPP-4 inhibitor. Risks were estimated using an inverse probability weighted pooled logistic regression model. Among 9691 metformin users, 154 developed HZ (weighted 4-year risk: 4.18%), while among 17 202 DPP-4 inhibitor users, 345 developed HZ (4.92%). The risk difference was −0.74% (95% CI, −1.80 to 0.39), and the risk ratio was 0.85 (95% CI, 0.66 to 1.08). In conclusion, metformin use did not reduce the 4-year risk of HZ compared with DPP-4 inhibitor use. This finding contradicts a prior observational report of a marked risk reduction, which was likely inflated by confounding by indication, and highlights the need to specify a clear causal estimand.

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二甲双胍预防日本2型糖尿病患者带状疱疹的有效性：一项目标试验模拟

2型糖尿病患者患带状疱疹（HZ）的风险较高。虽然二甲双胍可以通过免疫调节作用降低这种风险，但由于适应症的混淆和不明确的因果关系，先前的证据受到限制。我们的目的是评估与二肽基肽酶-4 （DPP-4）抑制剂相比，持续使用二甲双胍对HZ风险的per-protocol效应，没有证据表明二甲双胍会增加HZ风险。我们使用日本索赔数据库（2012年4月- 2023年12月）模拟了一项目标试验，以评估二甲双胍或DPP-4抑制剂新使用者的4年HZ风险。使用逆概率加权混合逻辑回归模型估计风险。9691名二甲双胍使用者中，154名发生HZ（加权4年风险：4.18%），而17202名DPP-4抑制剂使用者中，345名发生HZ（4.92%）。风险差异为- 0.74% (95% CI, - 1.80 ~ 0.39)，风险比为0.85 （95% CI, 0.66 ~ 1.08）。总之，与使用DPP-4抑制剂相比，使用二甲双胍并没有降低4年HZ的风险。这一发现与先前关于风险显著降低的观察性报告相矛盾，该报告可能因指示混淆而被夸大，并强调需要指定明确的因果估计。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of Medical Virology 医学-病毒学

CiteScore

23.20

自引率

2.40%

发文量

777

审稿时长

1 months

期刊介绍： The Journal of Medical Virology focuses on publishing original scientific papers on both basic and applied research related to viruses that affect humans. The journal publishes reports covering a wide range of topics, including the characterization, diagnosis, epidemiology, immunology, and pathogenesis of human virus infections. It also includes studies on virus morphology, genetics, replication, and interactions with host cells. The intended readership of the journal includes virologists, microbiologists, immunologists, infectious disease specialists, diagnostic laboratory technologists, epidemiologists, hematologists, and cell biologists. The Journal of Medical Virology is indexed and abstracted in various databases, including Abstracts in Anthropology (Sage), CABI, AgBiotech News & Information, National Agricultural Library, Biological Abstracts, Embase, Global Health, Web of Science, Veterinary Bulletin, and others.