Association between metformin use and progression of monoclonal gammopathy of undetermined significance to multiple myeloma in US veterans with diabetes mellitus: a population-based retrospective cohort study.
Association between metformin use and progression of monoclonal gammopathy of undetermined significance to multiple myeloma in US veterans with diabetes mellitus: a population-based retrospective cohort study.
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DOI：
10.1016/s2352-3026(14)00037-4
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发表时间：
2015-01
影响因子：
24.7
通讯作者：
Carson, Kenneth R.
中科院分区：
文献类型：
--
作者：
Chang, Su-Hsin;Luo, Suhong;O'Brian, Katiuscia K.;Thomas, Theodore S.;Colditz, Graham A.;Carlsson, Nils P.;Carson, Kenneth R.
多发性骨髓瘤（MM）是美国最常见的血液恶性肿瘤之一，并且之前一直伴有意义不明的单克隆丙种球蛋白病（MGUS）。确定了美国退伍军人健康管理局数据库中1999年10月1日至2009年12月31日期间诊断为MGUS和诊断为MGUS之前患有糖尿病的患者的回顾性队列，并随访至2013年8月6日。审查患者水平的临床数据，以验证诊断并提取关于基线M蛋白大小和MGUS类型的数据，即，免疫球蛋白（IG）亚型或轻链（当可用时）。二甲双胍使用者定义为接受二甲双胍处方至少4年，连续处方之间无单次中断≥ 6个月的患者。Kaplan-Meier曲线和考克斯模型用于分析二甲双胍使用与MGUS进展为MM之间的相关性。分析队列包括2，003例MGUS患者，中位随访时间为69个月。在分析队列中，确定了463名二甲双胍使用者（23.1%）。在二甲双胍使用者中，13例患者进展为MM，而在非二甲双胍使用者中，74例患者进展为MM。使用二甲双胍与转化为MM的风险降低相关（风险比，HR：0.47; 95%置信区间，CI：0.25 - 0.87）。对于诊断为MGUS的糖尿病患者，二甲双胍使用4年或更长时间与MGUS转化为MM的风险降低相关。需要进行前瞻性研究以确定这种关联是否是因果关系，以及这些结果是否可以外推至非糖尿病患者。
Multiple myeloma (MM) is one of the most common hematologic malignancies in the United States and is consistently preceded by monoclonal gammopathy of undetermined significance (MGUS). A retrospective cohort of patients in the U.S. Veterans Health Administration database diagnosed with MGUS between 1, October, 1999 and 31, December, 2009 and diabetes mellitus prior to their MGUS diagnosis was identified and followed through 6, August, 2013. Patient-level clinical data were reviewed to verify diagnoses and to abstract data on size of baseline M-protein and type of MGUS, i.e., immunoglobulin (Ig) subtype or light-chain, when available. Metformin users were defined as patients that were prescribed metformin for at least 4 years, with no single break between consecutive prescriptions ≥6 months. Kaplan-Meier curves and Cox models were used to analyze the association between metformin use and the progression of MGUS to MM. The analytic cohort consisted of 2,003 MGUS patients with a median follow-up time of 69 months. Within the analytic cohort, 463 metformin users (23·1%) were identified. Among the metformin users, 13 patients progressed to MM, while 74 patients progressed to MM among the non-metformin users. Metformin use was associated with a reduced risk of transformation to MM (Hazard ratio, HR: 0·47; 95% confidence interval, CI: 0·25–0·87). For diabetics diagnosed with MGUS, metformin use for 4 years or longer was associated with a reduced risk of transformation of MGUS to MM. Prospective studies are required to determine whether this association is causal and whether these results can be extrapolated to non-diabetics.