Acta oncologica (Stockholm, Sweden) · 2025
The risk of myelodysplastic syndrome and acute myeloid leukemia by metformin use and type 2 diabetes status - a Danish nation-wide cohort study.
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Rotbain Emelie C, Rostgaard Klaus, Kaastrup Katja, Mikkelsen Stine Ulrik, Hjalgrim Henrik, Grønbæk Kirsten
Аннотация
BACKGROUND AND PURPOSE: The treatment options for myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) have increased recently. However, drug resistance persists and patients who are ineligible for curative treatments still have a very poor prognosis. Previous studies support a general anti-neoplastic effect of metformin, and a recent preclinical investigation has shown that metformin may control the expansion of Dnmt3a clonal hematopoiesis, which is known to precede MDS and AML.
PATIENTS/MATERIAL AND METHODS: In this study we investigated the effect of metformin and type 2 diabetes (T2D) on the risk of developing MDS or AML. T2D was defined based on hospital diagnosis codes and glucose-lowering drug prescriptions. The study was performed as a cohort study with follow-up from 1 January 2000 to 31 December 2017 using Danish national, population-based register data.
RESULTS AND INTERPRETATION: In all, 6,031,132 persons contributed to the study of whom 302,403 had T2D, and 295,365 received metformin. Median follow-up time among individuals with T2D was more than 5 years, and among individuals without T2D more than 15 years. Our analyses revealed no association between T2D (hazard ratio [HR] 1.02 [95% confidence intervals (CI) 0.92-1.13]) or metformin use (HR 1.21 [95% CI 0.91-1.60]) and the risk of MDS or AML. However, when outcomes were studied separately, T2D was associated with an increased risk of MDS (HR 1.24 [95% CI 1.08-1.32]) but not with AML. Metformin use was not associated with MDS nor AML. Future studies should determine which patient groups may benefit from metformin to prevent MDS or AML development.
PATIENTS/MATERIAL AND METHODS: In this study we investigated the effect of metformin and type 2 diabetes (T2D) on the risk of developing MDS or AML. T2D was defined based on hospital diagnosis codes and glucose-lowering drug prescriptions. The study was performed as a cohort study with follow-up from 1 January 2000 to 31 December 2017 using Danish national, population-based register data.
RESULTS AND INTERPRETATION: In all, 6,031,132 persons contributed to the study of whom 302,403 had T2D, and 295,365 received metformin. Median follow-up time among individuals with T2D was more than 5 years, and among individuals without T2D more than 15 years. Our analyses revealed no association between T2D (hazard ratio [HR] 1.02 [95% confidence intervals (CI) 0.92-1.13]) or metformin use (HR 1.21 [95% CI 0.91-1.60]) and the risk of MDS or AML. However, when outcomes were studied separately, T2D was associated with an increased risk of MDS (HR 1.24 [95% CI 1.08-1.32]) but not with AML. Metformin use was not associated with MDS nor AML. Future studies should determine which patient groups may benefit from metformin to prevent MDS or AML development.