二甲双胍和他汀类药物联合治疗对降低前列腺癌风险有增强作用
发布时间：2011-07-03 10:18:51浏览次数：5849次来源：Monday, June 27, 2011: 1:00 PM - 2:00 PM Room: Hall B - Poster Hall ADA2011
二甲双胍（METF）和他汀类药物治疗可能具有癌症预防作用。本研究对复员军人用药卫生保健系统（VAHCS）的T2DM患者中两种主要的降糖药物METF和磺脲类药物（SU）相关的前列腺癌（PCa）危险性进行比较。此外，为了更好的了解今后的实验设计，他汀类药物的使用对METF对PCa发病率的作用是否有影响也进行了观察。本研究队列纳入VAHCS的5042名男性确诊为T2DM的患者，排除基线前确诊癌症的患者，在1999-2005年间使用METF或SU作为唯一降糖药物时间≥180天，没有基线时协变量的缺失。使用Cox比例危害分析评估由METF和/或他汀类药物导致的PCa发病率的危害比（HR），其中METF和他汀使用的倾向评分作为逆转可能权重进行校正，来解释药物组间基线时协变量的不平衡。表1列出了所有PCa相关变量（年龄，种族，合并疾病，吸烟史，BMI，HbA1c，LDL和糖尿病病程）。我们分析了METF和他汀的机制和剂量效应。平均LDL升高与高PCa发病率相关。大剂量更长时间的他汀治疗与PCa发病率降低相关。METF每日最大剂量>1000mg与PCa发病率降低有关(HR .45， p=0.0004)。基线时HbA1c较高与PCa危险性降低有关。这一矛盾可能提示胰岛素抵抗严重的患者从METF及他汀类药物治疗中获益更多，或者雄激素水平更低。总之，糖尿病患者中血脂异常发病率很高，METF和他汀类药物治疗对PCa发病率的作用可能相互增强。METF的独立作用有待于进一步观察，包括剂量，代谢及激素特征。
Abstract Body:
Treatment with metformin (METF) and statins have shown promise for cancer prevention trials. This study compared prostate cancer (PCa) risk associated with METF and sulfonylureas (SU), two predominating hypoglycemic agents in patients with T2DM in the Veteran Administration Health Care System (VAHCS). Further, to better inform future trial design, whether the effect of METF on PCa incidence was modified by statin use was examined. The study cohort consisted of 5042 male patients seen in VAHCS who were diagnosed for T2DM, without cancer diagnosed prior to the baseline, prescribed with either METF or SU as the exclusive hypoglycemic medication for ≥180 days between FY1999-FY2005, and with no missing baseline covariates. Mean follow-up was ∼ 5 yrs. Cox proportional hazard analyses were conducted to assess the hazard ratio (HR) of PCa incidence due to METF and/or statins, where propensity scores of METF and statin use were adjusted as inverse probability weights to account for imbalance in baseline covariates across medication groups. All variables associated with PCa (age, race/ethnicity, comorbidity, smoking, BMI, HbA1C, LDL and duration of diabetes) were accounted for.[table1]We explored mechanisms and dose effects of METF and statins. Higher mean LDL was associated with increased PCa incidence. A longer proportion of time on higher doses of statins was correlated with reduced PCa incidence. METF max daily dose >1000mg was assoc with lower PCa incidence (HR .45, p=0.0004). Higher baseline HbA1C was associated with decreased risk of PCa.This apparent paradox may reflect the possibility that subjects with greater insulin resistance benefit more from METFstatins or have lower androgen levels. In summary, in the diabetic population with high prevalence of dyslipidemia, the effect of METF and statin use on PCa incidence may be enhanced by one another. The independent effect of METF requires further investigation including accounting for dose, and metabolic and hormonal characteristics.
Category:
Clinical Therapeutics/New Technology - Pharmacologic Treatment of Diabetes or its Complications
| |
HR |
p-val |
|
HR |
| METF (no statin) |
1.58 |
<0.0001 |
METF (with statin) |
0.78 |
| Statin (no METF) |
0.54 |
<0.0001 |
Statin (with METF) |
0.27 |
| Interaction (METF and Statin) |
0.49 |
<0.0001 |
|
|
