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. 2024 Aug 27;8(16):4478-4485.
doi: 10.1182/bloodadvances.2023012266.

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

Daniel Tuyet Kristensen  1   2   3 , Andreas Kiesbye Øvlisen  1   2 , Lasse Hjort Kyneb Jakobsen  1 , Marianne Tang Severinsen  1   2 , Louise Hur Hannig  4 , Jørn Starklint  5 , Morten Hagemann Hilsøe  6 , Anders Pommer Vallentin  7 , Mette Brabrand  8 , Hans Carl Hasselbalch  9 , Tarec Christoffer El-Galaly  1   2   10   11 , Anne Stidsholt Roug  1   2   3
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Metformin use and risk of myeloproliferative neoplasms: a Danish population-based case-control study

Daniel Tuyet Kristensen et al. Blood Adv. .

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.

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Conflict of interest statement

Conflict-of-interest disclosure: D.T.K. serves as a member on consulting/advisory boards for AbbVie, Atheneum, and Astellas Pharma. H.C.H. is the chairman of the scientific committee for the INCA 33989-101 study (mCALR-101), Incyte; is a member on the advisory boards of AOP Orphan and Incyte; and is part of the scientific committee of Incyte. A.S.R. received consulting fees from AbbVie and Pfizer and a travel grant from Jazz Pharmaceuticals. The remaining authors declare no competing financial interests.

The current affiliation for L.H.K.J. is Novo Nordisk.

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