Population Health Department, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia; Prevention Division, Queensland Health, Brisbane, QLD, Australia.
Centre for Medicine Use and Safety (CMUS), Faculty of Pharmacy and Pharmaceutical Science, Monash University, Melbourne, VIC, Australia; School of Population and Global Health, Faculty of Medicine, Dentistry and Health Sciences, The University of Western Australia, Perth, WA, Australia.
Diabetes Res Clin Pract. 2021 May;175:108755. doi: 10.1016/j.diabres.2021.108755. Epub 2021 Apr 6.
Equivocal results of association between metformin and cancer-specific survival need more investigation. We tested the hypothesis that adherence to the drug had a lower cancer-specific mortality in a homogeneous population (i.e. regular users).
The Australian Cancer database was linked to the Pharmaceutical Benefits Scheme data and the National Death Index. Adherence to metformin was calculated by proportion of days covered. Cox regression models with time-varying covariates were used to estimate multivariable-adjusted cause-specific hazard ratios (HRs) and 95% confidence intervals (CI) for the association of adherence to metformin and cancer-specific mortality.
Between 2003 and 2013, three separate cohorts of 6717, 3121, and 1854 female patients were identified with newly diagnosed breast, colorectal, or endometrial cancer. The 1-year adherence was similar at baseline in three cohorts, on average 75%. Each 10% increase in 1-year adherence to metformin reduced cancer-specific mortality among women with breast cancer (adjusted HR = 0.95; 95% CI, 0.93-0.97), colorectal cancer (adjusted HR = 0.94; 95% CI, 0.91-0.96), or endometrial cancer (adjusted HR = 0.95; 95% CI, 0.90-0.99). The inverse associations remained unchanged in most subgroup analyses.
Among metformin users, adherence to this drug is inversely associated with reduced cancer-specific mortality. If confirmed, metformin could be considered as an adjuvant treatment.
二甲双胍与癌症特异性生存之间关联的结果存在不确定性，需要进一步研究。我们检验了一个假设，即在同质人群（即常规使用者）中，药物的依从性与较低的癌症特异性死亡率相关。
澳大利亚癌症数据库与药品福利计划数据和国家死亡索引相链接。通过覆盖天数的比例来计算二甲双胍的依从性。使用时变协变量的 Cox 回归模型来估计依从性与癌症特异性死亡率之间关联的多变量调整后的特定原因风险比（HR）和 95%置信区间（CI）。
在 2003 年至 2013 年期间，分别确定了 6717 例、3121 例和 1854 例新诊断为乳腺癌、结直肠癌或子宫内膜癌的女性患者的三个独立队列。三个队列的基线 1 年依从率相似，平均为 75%。1 年依从性每增加 10%，乳腺癌（调整 HR=0.95；95%CI，0.93-0.97）、结直肠癌（调整 HR=0.94；95%CI，0.91-0.96）或子宫内膜癌（调整 HR=0.95；95%CI，0.90-0.99）患者的癌症特异性死亡率降低。在大多数亚组分析中，这种反比关系仍然不变。
在二甲双胍使用者中，这种药物的依从性与降低的癌症特异性死亡率呈负相关。如果得到证实，二甲双胍可以被考虑作为一种辅助治疗。
