Shahrivar Mehrnoosh, Dietrich Caroline E, Glimelius Bengt, Saraste Deborah, Martling Anna, Buchli Christian, Nordenvall Caroline
Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
Clinical Epidemiology Division, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
Int J Cancer. 2025 May 1;156(9):1736-1745. doi: 10.1002/ijc.35266. Epub 2024 Nov 27.
Previous studies on the impact of metformin and colorectal cancer (CRC) outcomes have been limited by small size and confounding by indication, yielding inconsistent results. The aim of this study was to assess whether diabetes and pre-diagnostic metformin use influence CRC prognosis. The study was performed using the Colorectal Cancer Data Base Sweden, a register-linkage originating from the Swedish Colorectal Cancer Register with linkage to national health care registers and demographic registers. All adult patients diagnosed with primary non-metastatic CRC between 2007 and 2016, treated with curative surgery, were identified and followed up from 90 days post-surgery until December 31, 2022. Antidiabetic medication use was defined as dispensed prescription ≥6 months of use within 1 year of surgery. Type II diabetes mellitus (T2DM) patients were divided into three treatment groups (i) diet only, (ii) metformin user, and (iii) non-metformin user. Cox regression models estimated hazard ratios (HRs) with 95% confidence intervals (CIs) for time to recurrence, CRC-specific, and all-cause mortality, adjusted for relevant covariates. Of 33,028 non-metastatic CRC patients, 4539 (13.7%) had T2DM, with 1745 using metformin. A T2DM diagnosis was not associated with increased recurrence rate or CRC-specific mortality; HR 0.97 (95% CI 0.89-1.06) and HR 0.95 (95% CI 0.87-1.05), respectively, compared with non-diabetic patients. Furthermore, no association between T2DM, metformin use, and recurrence or CRC-specific mortality was seen, HR 0.98 (95% CI 0.86-1.12) and HR 0.98 (95% CI 0.85-1.13), respectively. T2DM is not associated with an elevated recurrence or CRC-specific mortality. Additionally, metformin use does not impact CRC prognosis.
以往关于二甲双胍对结直肠癌(CRC)预后影响的研究因样本量小和指征混杂而受到限制,结果并不一致。本研究的目的是评估糖尿病和诊断前使用二甲双胍是否会影响CRC的预后。该研究使用了瑞典结直肠癌数据库,这是一个源自瑞典结直肠癌登记处并与国家医疗保健登记处和人口登记处相链接的登记联动数据库。所有在2007年至2016年间被诊断为原发性非转移性CRC并接受根治性手术治疗的成年患者均被识别出来,并从术后90天开始随访至2022年12月31日。抗糖尿病药物的使用定义为在手术1年内有≥6个月的配药处方使用记录。II型糖尿病(T2DM)患者被分为三个治疗组:(i)仅饮食控制组,(ii)二甲双胍使用者组,(iii)非二甲双胍使用者组。Cox回归模型估计了复发时间、CRC特异性死亡率和全因死亡率的风险比(HRs)及其95%置信区间(CIs),并对相关协变量进行了调整。在33028例非转移性CRC患者中,4539例(13.7%)患有T2DM,其中1745例使用二甲双胍。T2DM诊断与复发率或CRC特异性死亡率的增加无关;与非糖尿病患者相比,HR分别为0.97(95%CI 0.89 - 1.06)和0.95(95%CI 0.87 - 1.05)。此外,未观察到T2DM、二甲双胍使用与复发或CRC特异性死亡率之间存在关联,HR分别为0.98(95%CI 0.86 - 1.12)和0.98(95%CI 0.85 - 1.13)。T2DM与复发率升高或CRC特异性死亡率无关。此外,二甲双胍的使用不会影响CRC的预后。