Kowall Bernd, Stang Andreas, Rathmann Wolfgang, Kostev Karel
Institute of Medical Informatics, Biometry and Epidemiology, Center of Clinical Epidemiology, University Hospital Essen, Essen, Germany.
German Diabetes Center, Institute of Biometrics and Epidemiology, Düsseldorf, Germany.
Pharmacoepidemiol Drug Saf. 2015 Aug;24(8):865-74. doi: 10.1002/pds.3823. Epub 2015 Jul 1.
In observational studies, a lower cancer risk was reported for patients with diabetes using metformin. However, many of these studies had shortcomings like time-related biases. We aimed to compare the incidence rate of any cancer and some selected cancer sites in metformin, sulfonylurea, and insulin users and to reduce some major biases common in observational studies.
In a retrospective database study, we used patient data from general practices throughout Germany and the UK. Eighty thousand two hundred and sixty-three patients aged 30-89 years at diagnosis of diabetes were observed for a mean follow-up of 4.8 years after the first antidiabetes medication. In Cox regression models adjusted for age, sex, country, metabolic factors, diabetes duration, medication, and comorbidity, patients who started using metformin were compared with those who started using sulfonylurea (or insulin) (intention-to-treat type analysis), and, additionally, patients with metformin monotherapy were compared with those with sulfonylurea (or insulin) monotherapy. The initial 12 months of follow-up after the first antidiabetes prescription were excluded.
Four thousand seven hundred seventy-nine (6.0%) incident cases of cancer were identified. Throughout all analyses, hazard ratios were close to the null for comparisons of metformin use with sulfonylurea and insulin use. For example, in intention-to-treat analyses comparing metformin with sulfonylurea use, hazard ratios were 1.05 (95%CI: 0.99-1.12) for any cancer, 1.05 (0.85-1.30) for colorectal, 1.04 (0.82-1.31) for lung, 1.03 (0.81-1.30) for breast, and 0.89 (0.73-1.08) for prostate cancer.
This study provides evidence that metformin has no protective effect on the incidence of cancer in persons with diabetes.
在观察性研究中,有报告称使用二甲双胍的糖尿病患者患癌风险较低。然而,这些研究中的许多都存在诸如时间相关偏倚等缺点。我们旨在比较二甲双胍、磺脲类药物和胰岛素使用者中任何癌症以及某些特定癌症部位的发病率,并减少观察性研究中常见的一些主要偏倚。
在一项回顾性数据库研究中,我们使用了来自德国和英国全科医疗的患者数据。观察了80263例诊断为糖尿病时年龄在30 - 89岁的患者,在首次使用抗糖尿病药物后的平均随访时间为4.8年。在根据年龄、性别、国家、代谢因素、糖尿病病程、药物治疗和合并症进行调整的Cox回归模型中,将开始使用二甲双胍的患者与开始使用磺脲类药物(或胰岛素)的患者进行比较(意向性治疗类型分析),此外,还将二甲双胍单药治疗的患者与磺脲类药物(或胰岛素)单药治疗的患者进行比较。首次抗糖尿病处方后的最初12个月随访被排除。
共识别出4779例(6.0%)癌症病例。在所有分析中,二甲双胍使用与磺脲类药物和胰岛素使用比较的风险比均接近无效值。例如,在意向性治疗分析中,比较二甲双胍与磺脲类药物使用时,任何癌症的风险比为1.05(95%置信区间:0.99 - 1.12),结直肠癌为1.05(0.85 - 1.30),肺癌为1.04(0.82 - 1.31),乳腺癌为1.03(0.81 - 1.30),前列腺癌为0.89(0.73 - 1.08)。
本研究提供的证据表明,二甲双胍对糖尿病患者的癌症发病率没有保护作用。