Diabetes, metformin use, and colon cancer: a population-based cohort study in Taiwan

Abstract

Objective: A retrospective cohort study, using a population-based reimbursement database, was conducted for investigating the relationship between diabetes and colon cancer and assessing whether metformin had a protective effect. Methods: Overall, 493 704 men and 502 139 women, covered by the National Health Insurance, without colon cancer were followed from 2003 to 2005. Cox regression evaluated the adjusted relative risk (RR), considering confounders and detection examinations. Results: Even though diabetes patients had a significantly higher probability of receiving examinations that could lead to the detection of colon cancer, they had a significantly higher risk (24%) of this cancer after adjustment. Metformin users had a significantly lower risk (27%) of colon cancer. While comparing patients with diabetes for !1, 1-3, and R3 years to nondiabetes individuals, the adjusted RR (95% confidence interval) was 1.308 (1.020-1.679), 1.087 (0.900-1.313), and 1.185 (1.055-1.330) respectively. The higher risk among those with diabetes for !1 year suggested a possible reverse causality or a link with prediabetes. However, diabetes still might play some role in the development of colon cancer in those with diabetes for R3 years. The duration of metformin use showed an inverse trend, with a significant RR of 0.643 (0.490-0.845) in users for R3 years, when compared with nonusers. In addition, metformin may reduce colon cancer risk associated with chronic obstructive pulmonary disease (a surrogate for smoking). Conclusions: Following adjustment for potential detection bias and other covariates, diabetes remains a significant risk factor for colon cancer. Metformin may protect against colon cancer.

The Effect of Metformin on Colorectal Carcinoma in Type 2 Diabetes Mellitus Patients: A Markov Model Analysis

“…Some previous observational and mechanistic studies show positive results [35][36][37]. However, no demonstrable protective effect of metformin against malignancy is shown in the RCT (OR=0.69, 95% CI: 0.26-1.82) [23].…”

“…Morbidity and mortality of CRC in type 2 diabetes mellitus (T2DM) patients are higher than that in the general population [5], since they have such risk factors in common as obesity, alcohol consumption and Western diet pattern and so on [6]. On exploring chemopreventive drugs against cancer, many studies, but not all, found that metformin, the typical first-line treatment for T2DM, reduced the incidence of many cancers, including CRC [7,8]. Nevertheless, some studies illustrated that metformin provided no protective effect against cancers, including CRC in T2DM patients [9,10].…”

Antidiabetic Medications and the Risk of Colorectal Cancer in Patients with Diabetes Mellitus: A Systematic Review and Meta-analysis

“…These studies cumulatively reported 13,871 colorectal cancer cases in 840,787 patients with diabetes mellitus. There were four Taiwanese studies from the same cohort (15,34,43,44), and hence, only one report was included in the main analysis (34). There were three studies that compared the association between insulin glargine (as compared with nonglargine insulin) and the risk of cancer, and these were excluded from analysis (45)(46)(47).…”

Metformin and Risk of Hypertension in Taiwanese Patients With Type 2 Diabetes Mellitus

“…The classifications of living region and occupation were detailed elsewhere 13. In brief, the living region was classified as Taipei, Northern, Central, Southern, and Kao‐Ping/Eastern.…”