Rotbain Emelie C, Rostgaard Klaus, Kaastrup Katja, Mikkelsen Stine Ulrik, Hjalgrim Henrik, Grønbæk Kirsten
Department of Hematology, Rigshospitalet, Copenhagen, Denmark; Hematology, Danish Cancer Institute, Danish Cancer Society, Copenhagen, Denmark.
Hematology, Danish Cancer Institute, Danish Cancer Society, Copenhagen, Denmark; Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark.
Acta Oncol. 2025 May 7;64:623-629. doi: 10.2340/1651-226X.2025.42422.
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.
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.
骨髓增生异常综合征（MDS）和急性髓系白血病（AML）的治疗选择近来有所增加。然而，耐药现象依然存在，无法接受根治性治疗的患者预后仍然很差。既往研究支持二甲双胍具有普遍的抗肿瘤作用，最近一项临床前研究表明，二甲双胍可能控制已知先于MDS和AML出现的Dnmt3a克隆性造血的扩增。
患者/材料与方法：在本研究中，我们调查了二甲双胍和2型糖尿病（T2D）对发生MDS或AML风险的影响。T2D根据医院诊断编码和降糖药物处方来定义。本研究作为一项队列研究进行，利用丹麦全国基于人群的登记数据，随访时间从2000年1月1日至2017年12月31日。
共有6,031,132人参与了本研究，其中302,403人患有T2D，以及295,365人使用了二甲双胍。T2D患者的中位随访时间超过5年，无T2D患者的中位随访时间超过15年。我们的分析显示，T2D（风险比[HR] 1.02 [95%置信区间（CI）0.92 - 1.13]）或二甲双胍使用（HR 1.21 [95% CI 0.91 - 1.60]）与MDS或AML风险之间无关联。然而，当分别研究结局时，T2D与MDS风险增加相关（HR 1.24 [95% CI 1.08 - 1.32]），但与AML无关。使用二甲双胍与MDS和AML均无关联。未来研究应确定哪些患者群体可能从二甲双胍预防MDS或AML发生中获益。
