Cancer risk among insulin users: comparing analogues with human insulin in the CARING five-country cohort study

Anna But; Marie L De Bruin; Marloes T Bazelier; Vidar Hjellvik; Morten Andersen; Anssi Auvinen; Jakob Starup-Linde; Marjanka K Schmidt; Kari Furu; Frank de Vries; Øystein Karlstad; Nils Ekström; Jari Haukka

doi:10.1007/s00125-017-4312-5

Cancer risk among insulin users: comparing analogues with human insulin in the CARING five-country cohort study

Anna But, Marie L De Bruin, Marloes T Bazelier, Vidar Hjellvik, Morten Andersen, Anssi Auvinen, Jakob Starup-Linde, Marjanka K Schmidt, Kari Furu, Frank de Vries, Øystein Karlstad, Nils Ekström, Jari Haukka

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Abstract

AIMS/HYPOTHESIS: The aim of this work was to investigate the relationship between use of certain insulins and risk for cancer, when addressing the limitations and biases involved in previous studies.

METHODS: National Health Registries from Denmark (1996-2010), Finland (1996-2011), Norway (2005-2010) and Sweden (2007-2012) and the UK Clinical Practice Research Datalink database (1987-2013) were used to conduct a cohort study on new insulin users (N = 327,112). By using a common data model and semi-aggregate approach, we pooled individual-level records from five cohorts and applied Poisson regression models. For each of ten cancer sites studied, we estimated the rate ratios (RRs) by duration (≤0.5, 0.5-1, 1-2, 2-3, 3-4, 4-5, 5-6 and >6 years) of cumulative exposure to insulin glargine or insulin detemir relative to that of human insulin.

RESULTS: A total of 21,390 cancer cases occurred during a mean follow-up of 4.6 years. No trend with cumulative treatment time for insulin glargine relative to human insulin was observed in risk for any of the ten studied cancer types. Of the 136 associations tested in the main analysis, only a few increased and decreased risks were found: among women, a higher risk was observed for colorectal (RR 1.54, 95% CI 1.06, 2.25) and endometrial cancer (RR 1.78, 95% CI 1.07, 2.94) for ≤0.5 years of treatment and for malignant melanoma for 2-3 years (RR 1.92, 95% CI 1.02, 3.61) and 4-5 years (RR 3.55, 95% CI 1.68, 7.47]); among men, a lower risk was observed for pancreatic cancer for 2-3 years (RR 0.34, 95% CI 0.17, 0.66) and for liver cancer for 3-4 years (RR 0.36, 95% CI 0.14, 0.94) and >6 years (RR 0.22, 95% CI 0.05, 0.92). Comparisons of insulin detemir with human insulin also showed no consistent differences.

CONCLUSIONS/INTERPRETATION: The present multi-country study found no evidence of consistent differences in risk for ten cancers for insulin glargine or insulin detemir use compared with human insulin, at follow-up exceeding 5 years.

Original language	English
Journal	Diabetologia
Volume	60
Issue number	9
Pages (from-to)	1691-1703
ISSN	0012-186X
DOIs	https://doi.org/10.1007/s00125-017-4312-5
Publication status	Published - 1 Sept 2017

Keywords

Journal Article

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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But, A., De Bruin, M. L., Bazelier, M. T., Hjellvik, V., Andersen, M., Auvinen, A., Starup-Linde, J., Schmidt, M. K., Furu, K., de Vries, F., Karlstad, Ø., Ekström, N., & Haukka, J. (2017). Cancer risk among insulin users: comparing analogues with human insulin in the CARING five-country cohort study. Diabetologia, 60(9), 1691-1703. https://doi.org/10.1007/s00125-017-4312-5

But, A, De Bruin, ML, Bazelier, MT, Hjellvik, V, Andersen, M, Auvinen, A, Starup-Linde, J, Schmidt, MK, Furu, K, de Vries, F, Karlstad, Ø, Ekström, N & Haukka, J 2017, 'Cancer risk among insulin users: comparing analogues with human insulin in the CARING five-country cohort study', Diabetologia, vol. 60, no. 9, pp. 1691-1703. https://doi.org/10.1007/s00125-017-4312-5

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title = "Cancer risk among insulin users: comparing analogues with human insulin in the CARING five-country cohort study",

abstract = "AIMS/HYPOTHESIS: The aim of this work was to investigate the relationship between use of certain insulins and risk for cancer, when addressing the limitations and biases involved in previous studies.METHODS: National Health Registries from Denmark (1996-2010), Finland (1996-2011), Norway (2005-2010) and Sweden (2007-2012) and the UK Clinical Practice Research Datalink database (1987-2013) were used to conduct a cohort study on new insulin users (N = 327,112). By using a common data model and semi-aggregate approach, we pooled individual-level records from five cohorts and applied Poisson regression models. For each of ten cancer sites studied, we estimated the rate ratios (RRs) by duration (≤0.5, 0.5-1, 1-2, 2-3, 3-4, 4-5, 5-6 and >6 years) of cumulative exposure to insulin glargine or insulin detemir relative to that of human insulin.RESULTS: A total of 21,390 cancer cases occurred during a mean follow-up of 4.6 years. No trend with cumulative treatment time for insulin glargine relative to human insulin was observed in risk for any of the ten studied cancer types. Of the 136 associations tested in the main analysis, only a few increased and decreased risks were found: among women, a higher risk was observed for colorectal (RR 1.54, 95% CI 1.06, 2.25) and endometrial cancer (RR 1.78, 95% CI 1.07, 2.94) for ≤0.5 years of treatment and for malignant melanoma for 2-3 years (RR 1.92, 95% CI 1.02, 3.61) and 4-5 years (RR 3.55, 95% CI 1.68, 7.47]); among men, a lower risk was observed for pancreatic cancer for 2-3 years (RR 0.34, 95% CI 0.17, 0.66) and for liver cancer for 3-4 years (RR 0.36, 95% CI 0.14, 0.94) and >6 years (RR 0.22, 95% CI 0.05, 0.92). Comparisons of insulin detemir with human insulin also showed no consistent differences.CONCLUSIONS/INTERPRETATION: The present multi-country study found no evidence of consistent differences in risk for ten cancers for insulin glargine or insulin detemir use compared with human insulin, at follow-up exceeding 5 years.",

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author = "Anna But and {De Bruin}, {Marie L} and Bazelier, {Marloes T} and Vidar Hjellvik and Morten Andersen and Anssi Auvinen and Jakob Starup-Linde and Schmidt, {Marjanka K} and Kari Furu and {de Vries}, Frank and {\O}ystein Karlstad and Nils Ekstr{\"o}m and Jari Haukka",

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doi = "10.1007/s00125-017-4312-5",

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T1 - Cancer risk among insulin users

T2 - comparing analogues with human insulin in the CARING five-country cohort study

AU - But, Anna

AU - De Bruin, Marie L

AU - Bazelier, Marloes T

AU - Hjellvik, Vidar

AU - Andersen, Morten

AU - Auvinen, Anssi

AU - Starup-Linde, Jakob

AU - Schmidt, Marjanka K

AU - Furu, Kari

AU - de Vries, Frank

AU - Karlstad, Øystein

AU - Ekström, Nils

AU - Haukka, Jari

PY - 2017/9/1

Y1 - 2017/9/1

N2 - AIMS/HYPOTHESIS: The aim of this work was to investigate the relationship between use of certain insulins and risk for cancer, when addressing the limitations and biases involved in previous studies.METHODS: National Health Registries from Denmark (1996-2010), Finland (1996-2011), Norway (2005-2010) and Sweden (2007-2012) and the UK Clinical Practice Research Datalink database (1987-2013) were used to conduct a cohort study on new insulin users (N = 327,112). By using a common data model and semi-aggregate approach, we pooled individual-level records from five cohorts and applied Poisson regression models. For each of ten cancer sites studied, we estimated the rate ratios (RRs) by duration (≤0.5, 0.5-1, 1-2, 2-3, 3-4, 4-5, 5-6 and >6 years) of cumulative exposure to insulin glargine or insulin detemir relative to that of human insulin.RESULTS: A total of 21,390 cancer cases occurred during a mean follow-up of 4.6 years. No trend with cumulative treatment time for insulin glargine relative to human insulin was observed in risk for any of the ten studied cancer types. Of the 136 associations tested in the main analysis, only a few increased and decreased risks were found: among women, a higher risk was observed for colorectal (RR 1.54, 95% CI 1.06, 2.25) and endometrial cancer (RR 1.78, 95% CI 1.07, 2.94) for ≤0.5 years of treatment and for malignant melanoma for 2-3 years (RR 1.92, 95% CI 1.02, 3.61) and 4-5 years (RR 3.55, 95% CI 1.68, 7.47]); among men, a lower risk was observed for pancreatic cancer for 2-3 years (RR 0.34, 95% CI 0.17, 0.66) and for liver cancer for 3-4 years (RR 0.36, 95% CI 0.14, 0.94) and >6 years (RR 0.22, 95% CI 0.05, 0.92). Comparisons of insulin detemir with human insulin also showed no consistent differences.CONCLUSIONS/INTERPRETATION: The present multi-country study found no evidence of consistent differences in risk for ten cancers for insulin glargine or insulin detemir use compared with human insulin, at follow-up exceeding 5 years.

AB - AIMS/HYPOTHESIS: The aim of this work was to investigate the relationship between use of certain insulins and risk for cancer, when addressing the limitations and biases involved in previous studies.METHODS: National Health Registries from Denmark (1996-2010), Finland (1996-2011), Norway (2005-2010) and Sweden (2007-2012) and the UK Clinical Practice Research Datalink database (1987-2013) were used to conduct a cohort study on new insulin users (N = 327,112). By using a common data model and semi-aggregate approach, we pooled individual-level records from five cohorts and applied Poisson regression models. For each of ten cancer sites studied, we estimated the rate ratios (RRs) by duration (≤0.5, 0.5-1, 1-2, 2-3, 3-4, 4-5, 5-6 and >6 years) of cumulative exposure to insulin glargine or insulin detemir relative to that of human insulin.RESULTS: A total of 21,390 cancer cases occurred during a mean follow-up of 4.6 years. No trend with cumulative treatment time for insulin glargine relative to human insulin was observed in risk for any of the ten studied cancer types. Of the 136 associations tested in the main analysis, only a few increased and decreased risks were found: among women, a higher risk was observed for colorectal (RR 1.54, 95% CI 1.06, 2.25) and endometrial cancer (RR 1.78, 95% CI 1.07, 2.94) for ≤0.5 years of treatment and for malignant melanoma for 2-3 years (RR 1.92, 95% CI 1.02, 3.61) and 4-5 years (RR 3.55, 95% CI 1.68, 7.47]); among men, a lower risk was observed for pancreatic cancer for 2-3 years (RR 0.34, 95% CI 0.17, 0.66) and for liver cancer for 3-4 years (RR 0.36, 95% CI 0.14, 0.94) and >6 years (RR 0.22, 95% CI 0.05, 0.92). Comparisons of insulin detemir with human insulin also showed no consistent differences.CONCLUSIONS/INTERPRETATION: The present multi-country study found no evidence of consistent differences in risk for ten cancers for insulin glargine or insulin detemir use compared with human insulin, at follow-up exceeding 5 years.

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DO - 10.1007/s00125-017-4312-5

M3 - Journal article

C2 - 28573394

SN - 0012-186X

VL - 60

SP - 1691

EP - 1703

JO - Diabetologia

JF - Diabetologia

IS - 9

ER -

Cancer risk among insulin users: comparing analogues with human insulin in the CARING five-country cohort study

Abstract

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