Metformin use and risk of myeloproliferative neoplasms: a Danish population–based case-control study

Daniel Tuyet Kristensen; Andreas Kiesbye Øvlisen; Lasse Hjort Kyneb Jakobsen; Marianne Tang Severinsen; Louise Hur Hannig; Jørn Starklint; Morten Hagemann Hilsøe; Anders Pommer Vallentin; Mette Brabrand; Hans Carl Hasselbalch; Tarec Christoffer El-Galaly; Anne Stidsholt Roug

doi:10.1182/bloodadvances.2023012266

Metformin use and risk of myeloproliferative neoplasms: a Danish population–based case-control study

Daniel Tuyet Kristensen, Andreas Kiesbye Øvlisen, Lasse Hjort Kyneb Jakobsen, Marianne Tang Severinsen, Louise Hur Hannig, Jørn Starklint, Morten Hagemann Hilsøe, Anders Pommer Vallentin, Mette Brabrand, Hans Carl Hasselbalch, Tarec Christoffer El-Galaly, Anne Stidsholt Roug^*

^*Corresponding author af dette arbejde

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avis › Tidsskriftartikel › Forskning › peer review

1 Citationer (Scopus)

Abstract

Previous studies have suggested that metformin has beneficial effects beyond its glucose-lowering properties, particularly in terms of its potential as an antineoplastic and cancer-preventive agent. In this study, we aimed to investigate the association between metformin use and the risk of myeloproliferative neoplasms (MPN). We conducted a population-based case-control study using Danish registers. Cases with MPN diagnosed between 2010 and 2018 were identified, and metformin use before the MPN diagnosis was ascertained. We compared metformin use among cases with MPN and an age- and sex-matched control group from the Danish general population to estimate age- and sex-adjusted odds ratios (ORs) and fully adjusted ORs (aORs) for the association between metformin use and risk of MPN. The study population included 3816 cases and 19 080 controls. Overall, 7.0% of cases and 8.2% of controls were categorized as ever-users of metformin, resulting in an OR for MPN of 0.84 (95% confidence interval [CI], 0.73-0.96) and an aOR of 0.70 (95% CI, 0.61-0.81). Long-term metformin use (≥5 years) was more infrequent and comprised 1.1% of cases and 2.0% of controls, resulting in an OR of 0.57 (95% CI, 0.42-0.79) and an aOR of 0.45 (95% CI, 0.33-0.63). A dose-response relationship was observed when cumulative duration of treatment was analyzed, and this was consistent in stratified analyses of sex, age, and MPN subtypes. In conclusion, metformin use was associated with significantly lower odds of an MPN diagnosis, indicating its potential cancer-preventive effect. Given the retrospective design, causality cannot be inferred.

Originalsprog	Engelsk
Tidsskrift	Blood Advances
Vol/bind	8
Nummer	16
Sider (fra-til)	4478-4485
Antal sider	8
ISSN	2473-9529
DOI	https://doi.org/10.1182/bloodadvances.2023012266
Status	Udgivet - aug. 2024

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10.1182/bloodadvances.2023012266Licens: CC BY-NC-ND

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Kristensen, D. T., Øvlisen, A. K., Jakobsen, L. H. K., Severinsen, M. T., Hannig, L. H., Starklint, J., Hilsøe, M. H., Vallentin, A. P., Brabrand, M., Hasselbalch, H. C., El-Galaly, T. C., & Roug, A. S. (2024). Metformin use and risk of myeloproliferative neoplasms: a Danish population–based case-control study. Blood Advances, 8(16), 4478-4485. https://doi.org/10.1182/bloodadvances.2023012266

@article{dd6ae754693e41c09eb56fb20a03a230,

title = "Metformin use and risk of myeloproliferative neoplasms: a Danish population–based case-control study",

abstract = "Previous studies have suggested that metformin has beneficial effects beyond its glucose-lowering properties, particularly in terms of its potential as an antineoplastic and cancer-preventive agent. In this study, we aimed to investigate the association between metformin use and the risk of myeloproliferative neoplasms (MPN). We conducted a population-based case-control study using Danish registers. Cases with MPN diagnosed between 2010 and 2018 were identified, and metformin use before the MPN diagnosis was ascertained. We compared metformin use among cases with MPN and an age- and sex-matched control group from the Danish general population to estimate age- and sex-adjusted odds ratios (ORs) and fully adjusted ORs (aORs) for the association between metformin use and risk of MPN. The study population included 3816 cases and 19 080 controls. Overall, 7.0% of cases and 8.2% of controls were categorized as ever-users of metformin, resulting in an OR for MPN of 0.84 (95% confidence interval [CI], 0.73-0.96) and an aOR of 0.70 (95% CI, 0.61-0.81). Long-term metformin use (≥5 years) was more infrequent and comprised 1.1% of cases and 2.0% of controls, resulting in an OR of 0.57 (95% CI, 0.42-0.79) and an aOR of 0.45 (95% CI, 0.33-0.63). A dose-response relationship was observed when cumulative duration of treatment was analyzed, and this was consistent in stratified analyses of sex, age, and MPN subtypes. In conclusion, metformin use was associated with significantly lower odds of an MPN diagnosis, indicating its potential cancer-preventive effect. Given the retrospective design, causality cannot be inferred.",

author = "Kristensen, {Daniel Tuyet} and {\O}vlisen, {Andreas Kiesbye} and Jakobsen, {Lasse Hjort Kyneb} and Severinsen, {Marianne Tang} and Hannig, {Louise Hur} and J{\o}rn Starklint and Hils{\o}e, {Morten Hagemann} and Vallentin, {Anders Pommer} and Mette Brabrand and Hasselbalch, {Hans Carl} and El-Galaly, {Tarec Christoffer} and Roug, {Anne Stidsholt}",

note = "Publisher Copyright: {\textcopyright} 2024 by The American Society of Hematology.",

year = "2024",

month = aug,

doi = "10.1182/bloodadvances.2023012266",

language = "English",

volume = "8",

pages = "4478--4485",

journal = "Blood Advances",

issn = "2473-9529",

publisher = "American Society of Hematology",

number = "16",

}

Kristensen, DT, Øvlisen, AK, Jakobsen, LHK, Severinsen, MT, Hannig, LH, Starklint, J, Hilsøe, MH, Vallentin, AP, Brabrand, M, Hasselbalch, HC, El-Galaly, TC & Roug, AS 2024, 'Metformin use and risk of myeloproliferative neoplasms: a Danish population–based case-control study', Blood Advances, bind 8, nr. 16, s. 4478-4485. https://doi.org/10.1182/bloodadvances.2023012266

Metformin use and risk of myeloproliferative neoplasms: a Danish population–based case-control study. / Kristensen, Daniel Tuyet; Øvlisen, Andreas Kiesbye; Jakobsen, Lasse Hjort Kyneb et al.
I: Blood Advances, Bind 8, Nr. 16, 08.2024, s. 4478-4485.

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avis › Tidsskriftartikel › Forskning › peer review

TY - JOUR

T1 - Metformin use and risk of myeloproliferative neoplasms

T2 - a Danish population–based case-control study

AU - Kristensen, Daniel Tuyet

AU - Øvlisen, Andreas Kiesbye

AU - Jakobsen, Lasse Hjort Kyneb

AU - Severinsen, Marianne Tang

AU - Hannig, Louise Hur

AU - Starklint, Jørn

AU - Hilsøe, Morten Hagemann

AU - Vallentin, Anders Pommer

AU - Brabrand, Mette

AU - Hasselbalch, Hans Carl

AU - El-Galaly, Tarec Christoffer

AU - Roug, Anne Stidsholt

PY - 2024/8

Y1 - 2024/8

N2 - Previous studies have suggested that metformin has beneficial effects beyond its glucose-lowering properties, particularly in terms of its potential as an antineoplastic and cancer-preventive agent. In this study, we aimed to investigate the association between metformin use and the risk of myeloproliferative neoplasms (MPN). We conducted a population-based case-control study using Danish registers. Cases with MPN diagnosed between 2010 and 2018 were identified, and metformin use before the MPN diagnosis was ascertained. We compared metformin use among cases with MPN and an age- and sex-matched control group from the Danish general population to estimate age- and sex-adjusted odds ratios (ORs) and fully adjusted ORs (aORs) for the association between metformin use and risk of MPN. The study population included 3816 cases and 19 080 controls. Overall, 7.0% of cases and 8.2% of controls were categorized as ever-users of metformin, resulting in an OR for MPN of 0.84 (95% confidence interval [CI], 0.73-0.96) and an aOR of 0.70 (95% CI, 0.61-0.81). Long-term metformin use (≥5 years) was more infrequent and comprised 1.1% of cases and 2.0% of controls, resulting in an OR of 0.57 (95% CI, 0.42-0.79) and an aOR of 0.45 (95% CI, 0.33-0.63). A dose-response relationship was observed when cumulative duration of treatment was analyzed, and this was consistent in stratified analyses of sex, age, and MPN subtypes. In conclusion, metformin use was associated with significantly lower odds of an MPN diagnosis, indicating its potential cancer-preventive effect. Given the retrospective design, causality cannot be inferred.

AB - Previous studies have suggested that metformin has beneficial effects beyond its glucose-lowering properties, particularly in terms of its potential as an antineoplastic and cancer-preventive agent. In this study, we aimed to investigate the association between metformin use and the risk of myeloproliferative neoplasms (MPN). We conducted a population-based case-control study using Danish registers. Cases with MPN diagnosed between 2010 and 2018 were identified, and metformin use before the MPN diagnosis was ascertained. We compared metformin use among cases with MPN and an age- and sex-matched control group from the Danish general population to estimate age- and sex-adjusted odds ratios (ORs) and fully adjusted ORs (aORs) for the association between metformin use and risk of MPN. The study population included 3816 cases and 19 080 controls. Overall, 7.0% of cases and 8.2% of controls were categorized as ever-users of metformin, resulting in an OR for MPN of 0.84 (95% confidence interval [CI], 0.73-0.96) and an aOR of 0.70 (95% CI, 0.61-0.81). Long-term metformin use (≥5 years) was more infrequent and comprised 1.1% of cases and 2.0% of controls, resulting in an OR of 0.57 (95% CI, 0.42-0.79) and an aOR of 0.45 (95% CI, 0.33-0.63). A dose-response relationship was observed when cumulative duration of treatment was analyzed, and this was consistent in stratified analyses of sex, age, and MPN subtypes. In conclusion, metformin use was associated with significantly lower odds of an MPN diagnosis, indicating its potential cancer-preventive effect. Given the retrospective design, causality cannot be inferred.

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U2 - 10.1182/bloodadvances.2023012266

DO - 10.1182/bloodadvances.2023012266

M3 - Journal article

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AN - SCOPUS:85203008649

SN - 2473-9529

VL - 8

SP - 4478

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JO - Blood Advances

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Metformin use and risk of myeloproliferative neoplasms: a Danish population–based case-control study

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