Background Metformin is among the most used anti-diabetic medications, due to its minimal toxicity, favorable safety profile, availability, and low cost. In addition to its role in diabetes management, metformin may also reduce cancer risk. Methods We conducted a comprehensive systematic review and meta-analysis investigating the association between metformin use and cancer risk, with evaluation by specific cancer type when able. Applicable studies were identified in PubMed/MEDLINE, Embase, Cochrane, Web of Science, and Scopus from inception through March 7, 2023. Metformin use categorized as ‘ever’ or ‘yes’, with cancer diagnosis as the outcome. Paper quality was evaluated using National Heart, Lung, and Blood Institute (NIH) guidelines and publication bias evaluated using Egger’s test and Begg’s test and funnel plot. Pooled RR estimates were calculated using random effects models and sensitivity analysis completed through leave-one-out cross-validation. Results One hundred and sixty-six studies with cancer incidence information were included in the meta-analysis. Reduced risk for overall cancer was observed in case-control (RR, 0.55; 95% CI, 0.30-0.80) and prospective cohort (RR, 0.65; 95% CI, 0.37-0.93) studies. Metformin use was associated with reduced gastrointestinal (RR, 0.79; 95%CI, 0.73-0.85), urologic (RR, 0.88; 95%CI, 0.78-0.99), and hematologic (RR, 0.87; 95%CI, 0.75-0.99) cancer risk. Significant publication bias was observed within the studies (Egger’s p < .001). Conclusions Metformin may be associated with a decreased risk for many cancer types, but high heterogeneity and risk for publication bias limit confidence in these results. Additional studies in non-diabetic populations are needed to better understand the utility of metformin in cancer prevention.

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二甲双胍使用与癌症发病率的关联：系统评价和荟萃分析

背景二甲双胍是最常用的抗糖尿病药物之一，因为其毒性最小、安全性良好、可用性高且成本低。二甲双胍除了在糖尿病管理中发挥作用外，还可以降低癌症风险。方法 我们进行了全面的系统回顾和荟萃分析，调查二甲双胍的使用与癌症风险之间的关联，并在可能的情况下按特定癌症类型进行评估。 PubMed/MEDLINE、Embase、Cochrane、Web of Science 和 Scopus 中确定了从开始到 2023 年 3 月 7 日的适用研究。二甲双胍的使用被分类为“曾经”或“是”，并以癌症诊断为结果。使用国家心肺血液研究所 (NIH) 指南评估论文质量，并使用 Egger 检验和 Begg 检验和漏斗图评估发表偏倚。使用随机效应模型和通过留一交叉验证完成的敏感性分析来计算汇总 RR 估计值。结果 荟萃分析中纳入了 166 项有关癌症发病率信息的研究。在病例对照（RR，0.55；95% CI，0.30-0.80）和前瞻性队列（RR，0.65；95% CI，0.37-0.93）研究中观察到总体癌症风险降低。二甲双胍的使用与胃肠道（RR，0.79；95%CI，0.73-0.85）、泌尿系统（RR，0.88；95%CI，0.78-0.99）和血液系统（RR，0.87；95%CI，0.75-0.99）减少相关）癌症风险。研究中观察到显着的发表偏倚（Egger's p < .001）。结论 二甲双胍可能与降低多种癌症类型的风险相关，但高度异质性和发表偏倚风险限制了这些结果的可信度。需要对非糖尿病人群进行更多研究，以更好地了解二甲双胍在癌症预防中的效用。