Long-term use of metformin is associated with a decreased risk for colorectal cancer in men with diabetes, according to a study published in Cancer Epidemiology, Biomarkers & Prevention.
This retrospective cohort study included participants in the Kaiser Permanente Northern California Diabetes Registry (KPNC) from 1994 and 1996. To qualify, participants had to be at least 40 years old at baseline, have a primary hospital diagnosis of diabetes, take at least 1 diabetes-related medication, have at least 2 outpatient visits for diabetes, and have a laboratory record of an abnormal HbA1c test. Participants were excluded if they had not been continuously enrolled in KPNC for at least 2 years prior to baseline or if they had previously used metformin. After screening, 47,351 individuals were included in the final cohort, and 21,524 of whom received metformin during follow-up.
The fully adjusted model showed no association between ever metformin use and risk for colorectal cancer (hazard ratio [HR] 0.90; 95% CI, 0.76–1.07), nor was a decreased risk shown with cumulative duration or recency. There was, however, a reduction in overall risk for long-term users (≥5.0 years; HR 0.78; 95% CI, 0.60–1.02), and reduced risk was also associated with higher doses of metformin (HR 0.67; 95% CI 0.45–0.98). Increasing duration of use was associated with a decreased risk for men (P trend=0.05; HR 0.65; 95% CI, 0.45–0.94 for ≥5.0 years of metformin use), but not women (P trend=0.98; HR 0.95; 95% CI, 0.65–1.38 ≥5.0 years of metformin use).
Study investigators conclude, “our study found an inverse association between metformin use and colorectal cancer risk. The decreased risk observed for long-term metformin use, particularly in men, and with a high cumulative dose of metformin needs to be confirmed in larger, well-characterized cohorts of persons with diabetes over an extended period of follow-up, accounting for time-related and other potential biases. Further prospective studies to evaluate the effect of metformin on colorectal cancer recurrence and adenoma formation are warranted.”
Bradley MC, Ferrara A, Achacoso N, Ehrlich SF, Quesenberry CP Jr, and Habel LA. A cohort study of metformin and colorectal cancer risk among patients with diabetes mellitus. Cancer Epidemiol Biomarkers Prev. 2018; 27(5):525-530.