The Different Association between Metformin and Sulfony- lurea Derivatives and the Risk of Cancer May be Confounded by Body Mass Index

Aim: Several studies in large databases suggest that in comparison to glucose-lowering sulfonylurea derivatives, metformin is associated with a reduced risk of cancer in patients with diabetes. As many databases miss relevant confounder data, our objective was to investigate whether the determinants age, body mass index (BMI), alcohol consumption, and renal function were associated with dispensing of either metformin or sulfonylurea derivatives as first drug therapy for type 2 diabetes mellitus while taking into account calendar time. Methods: We identified 639 incident metformin users and 934 incident sulfonylurea derivatives users in the Rotterdam Study, a prospective population-based cohort study. Associations were studied using logistic regression analyses. Results: After adjustment for all other determinants, starters with metformin had a statistically significantly higher BMI than starters with sulfonylurea derivatives (OR 1.19, 95% CI 1.04 – 1.37 for starters < July 1st 2000; OR 1.23, 95% CI 1.04 – 1.45 for starters ≥ July 1st 2000). Age, renal function, and alcohol consumption were not statistically significantly associated with the probability of dispensing metformin versus sulfonylurea derivative therapy as first drug therapy for type 2 diabetes mellitus. Conclusion: BMI is associated with a higher probability of dispensing of metformin as first drug therapy for type 2 diabetes mellitus in comparison to sulfonylurea derivatives. BMI is associated with the risk of cancer as well as the risk of type 2 diabetes mellitus. Therefore, in studies analyzing the association between the use of metformin or sulfonylurea derivatives and the risk of cancer, BMI should be considered as an essential co-variable. *Corresponding author: Bruno H. Stricker, Department of Epidemiology, Erasmus MC, P.O. Box 2040, 3000CA Rotterdam, the Netherlands, Tel: +31-10-7044958; Fax: +31-10-7044657; E-mail: [email protected]