Postdiagnostic metformin use and survival of patients with colorectal cancer: A Nationwide cohort study

Epidemiological evidence for the association between postdiagnostic metformin use and survival in patients with colorectal cancer (CRC) remains limited. Using the Taiwan Cancer Registry database, a cohort of 16,676 diabetic patients newly diagnosed with CRC from January 1, 2004 through December 31, 2014, followed until December 31, 2016, was identified. Postdiagnostic use of metformin (two or more prescriptions after CRC diagnosis) was defined as a time-dependent covariate with 6-month lag. Multivariate Cox regression model and stabilized inverse probability of treatment weighting (IPTW) were used to estimate adjusted effects of metformin on all-cause mortality and CRC-specific mortality during follow-up. A number of 11,438 (69%) received metformin after CRC diagnosis. Overall, 7,393 deaths, including 4,845 CRC-specific deaths, were observed during 64,322 person-years of follow-up. After adjustment for demographic and clinical covariates, metformin users had lower all-cause mortality than did nonusers (hazard ratio [HR], 0.42; 95% confidence interval [CI], 0.40-0.44) and lower CRC-specific mortality (HR, 0.41; 95% CI, 0.39-0.44). Similar but somewhat attenuated effects were observed after stabilized IPTW (HR for all-cause mortality, 0.56; 95% CI, 0.53-0.59; HR for CRC-specific mortality, 0.58; 95% CI, 0.55-0.61). Similar results were observed in stratified analyses of 2,112 patients with no prediagnostic metformin use and 14,564 patients with prediagnostic metformin use. Findings for both outcomes were consistent in multiple sensitivity analyses. Use of postdiagnostic metformin was associated with significantly lower all-cause mortality and CRC-specific mortality, regardless of prior metformin use. These findings support the use of metformin as an adjunct to standard care of diabetic patients with CRC.