Type II diabetes and metformin use does not affect colorectal cancer prognosis

Abstract

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_adj 0.97 (95% CI 0.89-1.06) and HR_adj 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_adj 0.98 (95% CI 0.86-1.12) and HR_adj 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.

Keywords: colorectal cancer; diabetes; metformin; pharmacoepidemiology; survival.

FIGURE 1

Flowchart of the nationwide cohort of 33,028 Swedish CRC patients diagnosed 2007–2016, with follow‐up until December 2022. CRC, colorectal cancer; n, number; T1DM, type 1 diabetes mellitus; T2DM, type 2 diabetes mellitus.