Metformin use and risk of colorectal adenoma after polypectomy in patients with type 2 diabetes mellitus.
Metformin use and risk of colorectal adenoma after polypectomy in patients with type 2 diabetes mellitus.
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DOI：
10.1158/1055-9965.epi-15-0559
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发表时间：
2015-11
期刊：
影响因子：
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通讯作者：
Doubeni CA
中科院分区：
文献类型：
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作者：
Marks AR;Pietrofesa RA;Jensen CD;Zebrowski A;Corley DA;Doubeni CA
现有文献表明，最常用的双胍类药物二甲双胍可能降低结直肠癌（CRC）的风险。由于大多数crc起源于癌前腺瘤，我们研究了二甲双胍是否降低了2型糖尿病患者息肉切除术后结直肠腺瘤的风险。对40-89岁Kaiser Permanente北加州患者进行回顾性队列研究，这些患者患有2型糖尿病，2000-2009年基线结肠镜检查发现≥1个腺瘤，从基线腺瘤诊断到2012年1-10年重复结肠镜检查。Cox模型评估了随访期间二甲双胍使用与随后腺瘤诊断之间的关系，控制了年龄、种族/民族、性别、体重指数和重复检查指征。研究纳入2412例患者，随访时间中位数为4.5年；累计而言，1117例（46%）患者在重复结肠镜检查中有≥1个腺瘤。与未接受糖尿病药物治疗的患者（n=1,578）相比，仅使用二甲双胍（n=457）与较低的腺瘤复发风险相关(校正风险比（HR)=0.76, 95%可信区间（CI）： 0.65-0.89），并且随着二甲双胍总剂量的增加，这种相关性更强(四分位数(Q) 1: HR=0.90, CI 0.72-1.12；Q2: hr =0.89, ci 0.70-1.12；Q3: hr =0.80 ci 0.63-1.01；Q4: HR=0.50 CI 0.42-0.60， p值为趋势<0.001)。敏感性分析的结果没有变化，包括仅评估基线3-10年期间的结果。我们的研究表明，二甲双胍在降低2型糖尿病患者息肉切除术后发生腺瘤的风险方面具有潜在的益处。二甲双胍可能通过减少癌前病变的形成来降低结直肠癌的风险，从而增强了其使用的潜在额外益处。
Existing literature suggests that metformin, the most commonly used biguanide, may lower colorectal cancer (CRC) risk. Because most CRCs originate in pre-cancerous adenomas, we examined whether metformin use lowered colorectal adenoma risk after polypectomy in patients with type-2 diabetes. Retrospective cohort study of 40-89-year-old Kaiser Permanente Northern California patients who had type-2 diabetes, and ≥1 adenoma detected at baseline colonoscopy during 2000-2009 and a repeat colonoscopy 1-10 years from baseline adenoma diagnosis through 2012. Cox models evaluated the association between metformin use during follow-up and subsequent adenoma diagnoses, controlling for age, race/ethnicity, sex, body mass index, and repeat examination indication. Study included 2,412 patients followed for a median of 4.5 years; cumulatively, 1,117 (46%) patients had ≥1 adenoma at repeat colonoscopy. Compared to patients not receiving diabetes medications (n=1,578), metformin-only use (n=457) was associated with lower adenoma recurrence risk (adjusted hazard ratio (HR)=0.76, 95% confidence interval (CI): 0.65-0.89), and the association was stronger with increasing total metformin dose (quartile (Q) 1: HR=0.90, CI 0.72–1.12; Q2: HR=0.89, CI 0.70-1.12; Q3: HR=0.80 CI 0.63–1.01; Q4: HR=0.50 CI 0.42–0.60, P-value for trend<0.001). Findings were unchanged in sensitivity analyses including evaluating only outcomes during the 3-10-year period from baseline. Our study suggests a potential benefit of metformin use in lowering the risk of subsequent adenomas after polypectomy in patients with type-2 diabetes. Metformin may lower CRC risk by reducing the formation of pre-cancerous lesions, reinforcing the potential additional benefits of its use.