Although Helicobacter pylori infection is the most important causative factor for gastric cancer (GC), H. pylori eradication alone does not completely eliminate the GC risk. In addition to H. pylori eradication, other risk factors for GC should be identified and targeted. Diabetes mellitus (DM) confers a 20% increased risk of GC, which could be mediated via several biological mechanisms including the stimulation of cell proliferation via hyperinsulinemia and increased insulingrowth factor production, the promotion of angiogenesis, and DNA damage. With a current global prevalence of 9.3% and a predicted rise to 10.2% by 2030, DM could contribute substantially to the burden of GC cases worldwide. Emerging evidence showed that metformin possesses chemopreventive effects via both direct (e.g., adenosine monophosphate-activated protein kinase activation and subsequent inhibition of the mammalian target of rapamycin pathway) and indirect (e.g., modulation of the interaction between tumor cells and their microenvironment and gut microbiota) pathways. A recent meta-analysis of observational studies showed that metformin use was associated with 24% lower GC risk. However, many available observational studies related to metformin effects suffered from biases including the failure to adjust for the H. pylori infection status and serial glycemic control and time-related biases. Future prospective studies addressing these pitfalls are needed.

中文翻译：

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二甲双胍对胃癌发展的化学预防作用。

虽然幽门螺杆菌感染是胃癌 (GC) 最重要的致病因素，但单独根除幽门螺杆菌并不能完全消除 GC 风险。除了幽门螺杆菌根除，应识别和定位其他 GC 风险因素。糖尿病 (DM) 使 GC 的风险增加 20%，这可能通过多种生物学机制介导，包括通过高胰岛素血症刺激细胞增殖和增加胰岛素生长因子的产生、促进血管生成和 DNA 损伤。目前全球患病率为 9.3%，预计到 2030 年将上升至 10.2%，DM 可能会大大增加全球 GC 病例的负担。新出现的证据表明，二甲双胍通过直接（例如，一磷酸腺苷激活蛋白激酶激活和随后抑制哺乳动物雷帕霉素途径靶标）和间接（例如，调节肿瘤细胞与其微环境和肠道微生物群之间的相互作用）途径。最近对观察性研究的一项荟萃​​分析表明，使用二甲双胍与 24% 的 GC 风险降低相关。然而，许多现有的与二甲双胍效应相关的观察性研究存在偏差，包括未能针对幽门螺杆菌感染状态和连续血糖控制和时间相关偏差。未来需要针对这些缺陷进行前瞻性研究。