Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2009 Sep;52(9):1732-44.
doi: 10.1007/s00125-009-1418-4. Epub 2009 Jun 30.

Risk of malignancies in patients with diabetes treated with human insulin or insulin analogues: a cohort study

L G Hemkens  1 , U Grouven, R Bender, C Günster, S Gutschmidt, G W Selke, P T Sawicki
Affiliations

Risk of malignancies in patients with diabetes treated with human insulin or insulin analogues: a cohort study

L G Hemkens et al. Diabetologia. 2009 Sep.

Abstract

Aims/hypothesis: The 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.

Methods: Data 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.

Results: A 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/interpretation: Considering 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.

PubMed Disclaimer

Figures

Fig. 1
Fig. 1
Flow diagram of the data analysed
Fig. 2
Fig. 2
HRs (solid line) and 95% confidence limits (dotted lines) for malignant neoplasms (a–c) and mortality (d–f) for aspart (a, d), lispro (b, e) and glargine (c, f) based on the final models shown in ESM 2 and ESM 3. Because of the interaction with dose, the HRs change with varying dose levels. For mortality, the final model includes an additional interaction of glargine with age. Therefore, the HR curve shown for glargine refers to a fixed age of 70 years. The curves are plotted between the 5% and the 95% quantiles of the observed data for each insulin analogue
See this image and copyright information in PMC

Comment in

References

    1. {'text': '', 'ref_index': 1, 'ids': [{'type': 'PubMed', 'value': '12096082', 'is_inner': True, 'url': 'https://pubmed.ncbi.nlm.nih.gov/12096082/'}]}
    2. Sandhu MS, Dunger DB, Giovannucci EL (2002) Insulin, insulin-like growth factor-I (IGF-I), IGF binding proteins, their biologic interactions, and colorectal cancer. J Natl Cancer Inst 94:972–980 - PubMed
    1. {'text': '', 'ref_index': 1, 'ids': [{'type': 'PubMed', 'value': '8959325', 'is_inner': True, 'url': 'https://pubmed.ncbi.nlm.nih.gov/8959325/'}]}
    2. Tran TT, Medline A, Bruce WR (1996) Insulin promotion of colon tumors in rats. Cancer Epidemiol Biomarkers Prev 5:1013–1015 - PubMed
    1. {'text': '', 'ref_index': 1, 'ids': [{'type': 'DOI', 'value': '10.1002/ijc.22717', 'is_inner': False, 'url': 'https://doi.org/10.1002/ijc.22717'}, {'type': 'PubMed', 'value': '17397032', 'is_inner': True, 'url': 'https://pubmed.ncbi.nlm.nih.gov/17397032/'}]}
    2. Larsson SC, Mantzoros CS, Wolk A (2007) Diabetes mellitus and risk of breast cancer: a meta-analysis. Int J Cancer 121:856–862 - PubMed
    1. {'text': '', 'ref_index': 1, 'ids': [{'type': 'DOI', 'value': '10.1007/s00125-006-0468-0', 'is_inner': False, 'url': 'https://doi.org/10.1007/s00125-006-0468-0'}, {'type': 'PubMed', 'value': '17021919', 'is_inner': True, 'url': 'https://pubmed.ncbi.nlm.nih.gov/17021919/'}]}
    2. Larsson SC, Orsini N, Brismar K, Wolk A (2006) Diabetes mellitus and risk of bladder cancer: a meta-analysis. Diabetologia 49:2819–2823 - PubMed
    1. {'text': '', 'ref_index': 1, 'ids': [{'type': 'PubMed', 'value': '16288121', 'is_inner': True, 'url': 'https://pubmed.ncbi.nlm.nih.gov/16288121/'}]}
    2. Larsson SC, Orsini N, Wolk A (2005) Diabetes mellitus and risk of colorectal cancer: a meta-analysis. J Natl Cancer Inst 97:1679–1687 - PubMed

MeSH terms