Use of insulin and insulin analogs and risk of cancer - systematic review and meta-analysis of observational studies

Oystein Karlstad; Jacob Starup-Linde; Peter Vestergaard; Vidar Hjellvik; Marloes T Bazelier; Marjanka K Schmidt; Morten Andersen; Anssi Auvinen; Jari Haukka; Kari Furu; Frank de Vries; Marie L De Bruin

doi:10.2174/15680266113136660067

Use of insulin and insulin analogs and risk of cancer - systematic review and meta-analysis of observational studies

Oystein Karlstad^*, Jacob Starup-Linde, Peter Vestergaard, Vidar Hjellvik, Marloes T Bazelier, Marjanka K Schmidt, Morten Andersen, Anssi Auvinen, Jari Haukka, Kari Furu, Frank de Vries, Marie L De Bruin

^*Corresponding author for this work

Research output: Contribution to journal › (Systematic) Review article › peer-review

Abstract

BACKGROUND: An association of insulin use and risk of cancer has been reported but evidence is conflicting and methodological issues have been identified.

OBJECTIVE: To summarize results regarding insulin use and cancer risk by a systematic review and meta-analysis of cohort and case-control studies examining risk of cancer associated with insulin use in patients with diabetes.

DATA SOURCES: Systematic literature search in 5 databases: PubMed, Embase, Web of Science, Scopus and Cochrane Library. STUDY ELIGIBILITY CRITERIA (PICOS):

POPULATION: diabetes patients.

EXPOSURE: Users of any exogenous insulin. Comparison: Diabetes patients with or without use of antidiabetic drugs.

OUTCOME: Any incident cancer.

STUDY DESIGN: Cohort and case-control studies.

RESULTS: 42 eligible studies examined risk of any cancer and 27 site-specific cancers. Results of individual studies were heterogeneous. Meta-analyses were significant for: Insulin vs No Insulin: Increased risk for pancreas, liver, kidney, stomach and respiratory cancer, decreased risk for prostate cancer. Insulin vs Non-Insulin Antidiabetics: Increased risk for any, pancreatic and colorectal cancer. Glargine vs Non-Glargine Insulin: Increased risk for breast cancer, decreased risk for colon cancer.

LIMITATIONS: Few studies available for most cancer sites and exposure contrasts, and few assess effect of dose and duration of exposure. Methodological issues in several studies. Availability of confounders.

CONCLUSIONS: Insulin use was associated with risk of cancer at several sites. Cautious interpretation of results is warranted as methodological issues and limitations in several of the included studies have been identified. Choice of study design may have a profound effect on estimated cancer risk.

Original language	English
Pages (from-to)	333-48
Number of pages	16
Journal	Current Drug Safety
Volume	8
Issue number	5
DOIs	https://doi.org/10.2174/15680266113136660067
Publication status	Published - Nov 2013

Keywords

Breast Neoplasms/chemically induced
Case-Control Studies
Cohort Studies
Colorectal Neoplasms/chemically induced
Diabetes Mellitus/drug therapy
Female
Humans
Hypoglycemic Agents/adverse effects
Insulin/adverse effects
Insulin Glargine
Insulin, Long-Acting/adverse effects
Neoplasms/epidemiology
Observational Studies as Topic
Publication Bias
Registries
Research Design

Access to Document

10.2174/15680266113136660067Licence: Unspecified

Cite this

Karlstad, O., Starup-Linde, J., Vestergaard, P., Hjellvik, V., Bazelier, M. T., Schmidt, M. K., Andersen, M., Auvinen, A., Haukka, J., Furu, K., de Vries, F., & De Bruin, M. L. (2013). Use of insulin and insulin analogs and risk of cancer - systematic review and meta-analysis of observational studies. Current Drug Safety, 8(5), 333-48. https://doi.org/10.2174/15680266113136660067

@article{1fd7c5c1e8a349f9adb3099740328f04,

title = "Use of insulin and insulin analogs and risk of cancer - systematic review and meta-analysis of observational studies",

abstract = "BACKGROUND: An association of insulin use and risk of cancer has been reported but evidence is conflicting and methodological issues have been identified.OBJECTIVE: To summarize results regarding insulin use and cancer risk by a systematic review and meta-analysis of cohort and case-control studies examining risk of cancer associated with insulin use in patients with diabetes.DATA SOURCES: Systematic literature search in 5 databases: PubMed, Embase, Web of Science, Scopus and Cochrane Library. STUDY ELIGIBILITY CRITERIA (PICOS):POPULATION: diabetes patients.EXPOSURE: Users of any exogenous insulin. Comparison: Diabetes patients with or without use of antidiabetic drugs.OUTCOME: Any incident cancer.STUDY DESIGN: Cohort and case-control studies.RESULTS: 42 eligible studies examined risk of any cancer and 27 site-specific cancers. Results of individual studies were heterogeneous. Meta-analyses were significant for: Insulin vs No Insulin: Increased risk for pancreas, liver, kidney, stomach and respiratory cancer, decreased risk for prostate cancer. Insulin vs Non-Insulin Antidiabetics: Increased risk for any, pancreatic and colorectal cancer. Glargine vs Non-Glargine Insulin: Increased risk for breast cancer, decreased risk for colon cancer.LIMITATIONS: Few studies available for most cancer sites and exposure contrasts, and few assess effect of dose and duration of exposure. Methodological issues in several studies. Availability of confounders.CONCLUSIONS: Insulin use was associated with risk of cancer at several sites. Cautious interpretation of results is warranted as methodological issues and limitations in several of the included studies have been identified. Choice of study design may have a profound effect on estimated cancer risk.",

keywords = "Breast Neoplasms/chemically induced, Case-Control Studies, Cohort Studies, Colorectal Neoplasms/chemically induced, Diabetes Mellitus/drug therapy, Female, Humans, Hypoglycemic Agents/adverse effects, Insulin/adverse effects, Insulin Glargine, Insulin, Long-Acting/adverse effects, Neoplasms/epidemiology, Observational Studies as Topic, Publication Bias, Registries, Research Design",

author = "Oystein Karlstad and Jacob Starup-Linde and Peter Vestergaard and Vidar Hjellvik and Bazelier, {Marloes T} and Schmidt, {Marjanka K} and Morten Andersen and Anssi Auvinen and Jari Haukka and Kari Furu and {de Vries}, Frank and {De Bruin}, {Marie L}",

year = "2013",

month = nov,

doi = "10.2174/15680266113136660067",

language = "English",

volume = "8",

pages = "333--48",

journal = "Current Drug Safety",

issn = "1574-8863",

publisher = "Bentham Science Publishers",

number = "5",

}

Karlstad, O, Starup-Linde, J, Vestergaard, P, Hjellvik, V, Bazelier, MT, Schmidt, MK, Andersen, M, Auvinen, A, Haukka, J, Furu, K, de Vries, F & De Bruin, ML 2013, 'Use of insulin and insulin analogs and risk of cancer - systematic review and meta-analysis of observational studies', Current Drug Safety, vol. 8, no. 5, pp. 333-48. https://doi.org/10.2174/15680266113136660067

TY - JOUR

T1 - Use of insulin and insulin analogs and risk of cancer - systematic review and meta-analysis of observational studies

AU - Karlstad, Oystein

AU - Starup-Linde, Jacob

AU - Vestergaard, Peter

AU - Hjellvik, Vidar

AU - Bazelier, Marloes T

AU - Schmidt, Marjanka K

AU - Andersen, Morten

AU - Auvinen, Anssi

AU - Haukka, Jari

AU - Furu, Kari

AU - de Vries, Frank

AU - De Bruin, Marie L

PY - 2013/11

Y1 - 2013/11

N2 - BACKGROUND: An association of insulin use and risk of cancer has been reported but evidence is conflicting and methodological issues have been identified.OBJECTIVE: To summarize results regarding insulin use and cancer risk by a systematic review and meta-analysis of cohort and case-control studies examining risk of cancer associated with insulin use in patients with diabetes.DATA SOURCES: Systematic literature search in 5 databases: PubMed, Embase, Web of Science, Scopus and Cochrane Library. STUDY ELIGIBILITY CRITERIA (PICOS):POPULATION: diabetes patients.EXPOSURE: Users of any exogenous insulin. Comparison: Diabetes patients with or without use of antidiabetic drugs.OUTCOME: Any incident cancer.STUDY DESIGN: Cohort and case-control studies.RESULTS: 42 eligible studies examined risk of any cancer and 27 site-specific cancers. Results of individual studies were heterogeneous. Meta-analyses were significant for: Insulin vs No Insulin: Increased risk for pancreas, liver, kidney, stomach and respiratory cancer, decreased risk for prostate cancer. Insulin vs Non-Insulin Antidiabetics: Increased risk for any, pancreatic and colorectal cancer. Glargine vs Non-Glargine Insulin: Increased risk for breast cancer, decreased risk for colon cancer.LIMITATIONS: Few studies available for most cancer sites and exposure contrasts, and few assess effect of dose and duration of exposure. Methodological issues in several studies. Availability of confounders.CONCLUSIONS: Insulin use was associated with risk of cancer at several sites. Cautious interpretation of results is warranted as methodological issues and limitations in several of the included studies have been identified. Choice of study design may have a profound effect on estimated cancer risk.

AB - BACKGROUND: An association of insulin use and risk of cancer has been reported but evidence is conflicting and methodological issues have been identified.OBJECTIVE: To summarize results regarding insulin use and cancer risk by a systematic review and meta-analysis of cohort and case-control studies examining risk of cancer associated with insulin use in patients with diabetes.DATA SOURCES: Systematic literature search in 5 databases: PubMed, Embase, Web of Science, Scopus and Cochrane Library. STUDY ELIGIBILITY CRITERIA (PICOS):POPULATION: diabetes patients.EXPOSURE: Users of any exogenous insulin. Comparison: Diabetes patients with or without use of antidiabetic drugs.OUTCOME: Any incident cancer.STUDY DESIGN: Cohort and case-control studies.RESULTS: 42 eligible studies examined risk of any cancer and 27 site-specific cancers. Results of individual studies were heterogeneous. Meta-analyses were significant for: Insulin vs No Insulin: Increased risk for pancreas, liver, kidney, stomach and respiratory cancer, decreased risk for prostate cancer. Insulin vs Non-Insulin Antidiabetics: Increased risk for any, pancreatic and colorectal cancer. Glargine vs Non-Glargine Insulin: Increased risk for breast cancer, decreased risk for colon cancer.LIMITATIONS: Few studies available for most cancer sites and exposure contrasts, and few assess effect of dose and duration of exposure. Methodological issues in several studies. Availability of confounders.CONCLUSIONS: Insulin use was associated with risk of cancer at several sites. Cautious interpretation of results is warranted as methodological issues and limitations in several of the included studies have been identified. Choice of study design may have a profound effect on estimated cancer risk.

KW - Breast Neoplasms/chemically induced

KW - Case-Control Studies

KW - Cohort Studies

KW - Colorectal Neoplasms/chemically induced

KW - Diabetes Mellitus/drug therapy

KW - Female

KW - Humans

KW - Hypoglycemic Agents/adverse effects

KW - Insulin/adverse effects

KW - Insulin Glargine

KW - Insulin, Long-Acting/adverse effects

KW - Neoplasms/epidemiology

KW - Observational Studies as Topic

KW - Publication Bias

KW - Registries

KW - Research Design

U2 - 10.2174/15680266113136660067

DO - 10.2174/15680266113136660067

M3 - (Systematic) Review article

C2 - 24215311

SN - 1574-8863

VL - 8

SP - 333

EP - 348

JO - Current Drug Safety

JF - Current Drug Safety

IS - 5

ER -