Risk of malignancies in patients with diabetes treated with human insulin or insulin analogues: a cohort study
By L. Hemkens, U. Grouven, Ruben R. Bender, C. Günster, S. Gutschmidt, G. Selke, P. Sawicki. Diabetologia, 2009
634 citations recorded by the source corpus.
Aims/hypothesisThe aim of this cohort study was to investigate the risk of malignant neoplasms and mortality in patients with diabetes treated either with human insulin or with one of three insulin analogues.MethodsData were provided by the largest German statutory health insurance fund (time-frame: January 1998 to June 2005 inclusive), on patients without known malignant disease who had received first-time therapy for diabetes mellitus exclusively with human insulin, aspart, lispro or glargine. The primary outcome was the diagnosis of a malignant neoplasm. Data were analysed by multiple Cox regression models adjusting for potential confounders.ResultsA total of 127,031 patients were included, with a mean follow-up time of 1.63 (median 1.41, maximum 4.41) years. A positive association between cancer incidence and insulin dose was found for all insulin types. Because patients receiving combined therapy with insulin analogues and human insulin were excluded, the mean daily dose was much lower for glargine than for human insulin, and a slightly lower cancer incidence in the glargine group was found. After adjusting for dose, a dose-dependent increase in cancer risk was found for treatment with glargine compared with human insulin (p < 0.0001): the adjusted HR was 1.09 (95% CI 1.00 to 1.19) for a daily dose of 10 IU, 1.19 (95% CI 1.10 to 1.30) for a daily dose of 30 IU, and 1.31 (95% CI 1.20 to 1.42) for a daily dose of 50 IU. No increased risk was found for aspart (p = 0.30) or lispro (p = 0.96) compared with human insulin.Conclusions/interpretationConsidering the overall relationship between insulin dose and cancer, and the lower dose with glargine, the cancer incidence with glargine was higher than expected compared with human insulin. Our results based on observational data support safety concerns surrounding the mitogenic properties of glargine in diabetic patients. Prospective long-term studies are needed to further evaluate the safety of insulin analogues, especially glargine.
Subfields: Molecular Biology, Oncology
View Paper: https://www.semanticscholar.org/paper/c10c23cf482442b4779e95193097515b7ed34c65
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Citations in the corpus
- Diabetes and Cancer (2010, neutral): “Recently, a series of widely publicized epidemiologic analyses examined a possible association between insulin use and/or use of the long-acting insulin analog glargine (91,110,113,114) and an increase in risk of cancer.”
- Obesity and Diabetes: The Increased Risk of Cancer and Cancer-Related Mortality. (2015, background): “Human registry studies and retrospective cohort studies published in 2011–2012 reported that other insulin analogs may increase the risk of certain cancers, including breast cancer (74, 165, 179).”
- Shared Risk Factors in Cardiovascular Disease and Cancer (2016, result): “In contrast, a potential increased risk is associated with insulin analogues.(87,88) The general patterns demonstrated across several studies support the hyperinsulinemia hypothesis, where therapies that increase circulating insulin levels increase cancer risk, and those that lower insulin resistanc”