Insulin use and cancer risk in patients with type 2 diabetes: A systematic review and meta-analysis of observational studies

Aims. - To determine whether data from observational studies supports the hypothesis of an increased risk of overall and site-specific cancer among individuals with diabetes using exogenous insulin therapies. Methods. - We conducted a comprehensive search of nine key biomedical databases for all years up to December 2011, restricted to the English language. Data from cohort and nested case-control studies were included in random effects meta-analyses of site-specific and overall cancer incidence comparing ever use and new use of: (1) insulin to no insulin and; (2) insulin glargine to other insulins. Results. - The search yielded 3052 unique citations, of which 19 were selected for inclusion, representing data for 1,332,120 people and 41,947 cancers. Pancreatic cancer risk was increased among new users of insulin (RR: 3.18, 95%CI: 3.27-3.71, I-2=32%). New use of insulin glargine was associated with an increased risk of pancreatic cancer (RR: 1.63, 95%CI: 1.05-2.51, I-2 = 0%) and prostate cancers (RR: 2.68, 95%CI: 1.50-4.79, I-2 = 0%) but a decreased risk of colorectal cancer (RR: 0.78, 95%CI: 0.64-0.94, I-2 = 15%). Conclusion. - New use of insulin or insulin glargine was associated with an increased risk of pancreatic cancer, possibly due to reverse causality. New use of insulin glargine was associated with a decreased risk of colorectal cancer but an increased risk of prostate cancer. Our results should be interpreted with caution due to limitations of included studies. (C) 2012 Elsevier Masson SAS. All rights reserved.