Use of metformin is not associated with a decreased risk of colorectal cancer: a case-control analysis

Background: To explore the association between use of metformin or other antidiabetic drugs and the risk of colorectal cancer.

Methods: Using the United Kingdom-based General Practice Research Database (GPRD), we conducted a nested case-control analysis in patients with diabetes mellitus. Cases had an incident diagnosis of colorectal cancer, and up to 6 controls per case were matched on age, sex, calendar time, general practice, and number of years of active history in the GPRD prior to the index date. Results were adjusted for multiple potential confounders.

Results: We identified 920 diabetic patients with colorectal cancer. Mean age ± SD was 70.2 ± 8.6 years and 63.3% were male. Extensive use (≥50 prescriptions) of metformin was associated with a slightly increased risk of colorectal cancer (adjusted OR = 1.43, 95% CI: 1.08-1.90) as compared with non use, with an adjustment of OR = 1.81 (95% CI: 1.25-2.62) in men and of 1.00 (95% CI: 0.63-1.58) in women. Neither extensive use of sulfonylureas (adjusted OR = 0.79, 95% CI: 0.60-1.03) nor insulin (adjusted OR = 0.90, 95% CI: 0.63-1.28) were associated with an increased risk of colorectal cancer. A long-term history of diabetes (>10 years) was not associated with a materially increased risk of colorectal cancer compared with short-term diabetes duration (<2 years; adjusted OR = 1.14, 95% CI: 0.90-1.46).

Conclusion: Use of metformin was linked to an increased risk of colorectal cancer in men. Use of sulfonylureas or insulin was not associated with an altered risk of colorectal cancer.

Impact: Metformin does not prevent colorectal cancer.