Abstract
BACKGROUND: Existing literature suggests that metformin, the most commonly used biguanide, may lower colorectal cancer risk. Because most colorectal cancers originate in precancerous adenomas, we examined whether metformin use lowered colorectal adenoma risk after polypectomy in patients with type-2 diabetes. METHODS: Retrospective cohort study of 40- to 89-year-old Kaiser Permanente Northern California patients who had type 2 diabetes, and ≥1 adenoma detected at baseline colonoscopy during 2000 to 2009 and a repeat colonoscopy 1 to 10 years from baseline adenoma diagnosis through 2012. Cox models evaluated the association between metformin use during follow-up and subsequent adenoma diagnoses, controlling for age, race/ethnicity, sex, body mass index, and repeat examination indication. RESULTS: Study included 2,412 patients followed for a median of 4.5 years; cumulatively, 1,117 (46%) patients had ≥1 adenoma at repeat colonoscopy. Compared with patients not receiving diabetes medications (n = 1,578), metformin-only use (n = 457) was associated with lower adenoma recurrence risk [adjusted HR, 0.76; 95% confidence interval (CI), 0.65-0.89], and the association was stronger with increasing total metformin dose [quartile (Q) 1: HR, 0.90; 95% CI, 0.72-1.12; Q2: HR, 0.89; 95% CI, 0.70-1.12; Q3: HR, 0.80; 95% CI, 0.63-1.01; Q4: HR, 0.50; 95% CI, 0.42-0.60, Ptrend < 0.001]. Findings were unchanged in sensitivity analyses, including evaluating only outcomes during the 3- to 10-year period from baseline. CONCLUSION: Our study suggests a potential benefit of metformin use in lowering the risk of subsequent adenomas after polypectomy in patients with type 2 diabetes. IMPACT: Metformin may lower colorectal cancer risk by reducing the formation of precancerous lesions, reinforcing the potential additional benefits of its use.