Division of Urology, Duke Cancer Institute, Durham, NC; Department of Urology, Shiraz University of Medical Sciences, Shiraz, Iran.
Urology Section, Department of Surgery, Veterans Affairs Medical Center, Durham, NC.
Clin Genitourin Cancer. 2019 Feb;17(1):e140-e149. doi: 10.1016/j.clgc.2018.09.020. Epub 2018 Oct 4.
To investigate the preoperative use of combination metformin and statin versus monotherapy on biochemical recurrence (BCR) after radical prostatectomy (RP) in diabetic men.
Data of 843 diabetic men who underwent RP were stratified on the basis of preoperative use of no drug or of metformin, statin, or both. Multivariable Cox models were used to test the association between treatment and BCR. In a secondary analysis, models were stratified by race and body mass index (BMI) and further adjusted for glycated hemoglobin (HbA1c).
A total of 259 men (31%) received statin therapy, 94 (11%) metformin, 307 (36%) metformin + statin, and 183 (22%) neither. Five-year BCR-free survival rates were 75% in metformin only versus 75% in metformin + statin versus 60% in statin versus 68% in no drug groups (log-rank, P = .003). On multivariable analysis, preoperative statin use was associated with increased BCR risk versus men receiving neither drug (hazard ratio [HR] = 1.84; 95% confidence interval [CI], 1.28-2.64). Metformin alone (HR 0.88; 95% CI, 0.53-1.47) and metformin + statin (HR 0.88; 95% CI, 0.58-1.33) were unrelated to BCR risks. In secondary analysis, the association between statin use and higher BCR risk was similar regardless of race, but was stronger among men with BMI ≥ 30 kg/m (HR 3.12; 95% CI, 1.70-5.72). These results were largely unchanged after adjusting for HbA1c.
Among diabetic men undergoing RP, preoperative statin use was associated with worse BCR risk, especially among men with a high BMI, but these associations may be mitigated by concomitant use of metformin. If validated in future findings, research is needed to understand the basis for these associations.
研究糖尿病男性接受根治性前列腺切除术(RP)前联合使用二甲双胍和他汀类药物与单一药物治疗对生化复发(BCR)的影响。
根据术前是否使用药物、二甲双胍、他汀类药物或两者联合,对 843 名接受 RP 的糖尿病男性患者的数据进行分层。使用多变量 Cox 模型检验治疗与 BCR 之间的关联。在二次分析中,根据种族和体重指数(BMI)对模型进行分层,并进一步调整糖化血红蛋白(HbA1c)。
共有 259 名男性(31%)接受他汀类药物治疗,94 名(11%)接受二甲双胍治疗,307 名(36%)接受二甲双胍联合他汀类药物治疗,183 名(22%)未使用药物。仅使用二甲双胍、二甲双胍联合他汀类药物、他汀类药物和未使用药物组的 5 年 BCR 无复发生存率分别为 75%、75%、60%和 68%(对数秩检验,P=0.003)。多变量分析显示,与未使用药物的男性相比,术前使用他汀类药物与 BCR 风险增加相关(风险比[HR] = 1.84;95%置信区间[CI],1.28-2.64)。仅使用二甲双胍(HR 0.88;95% CI,0.53-1.47)和二甲双胍联合他汀类药物(HR 0.88;95% CI,0.58-1.33)与 BCR 风险无关。在二次分析中,无论种族如何,他汀类药物使用与更高的 BCR 风险之间的关联相似,但在 BMI≥30 kg/m²的男性中更为明显(HR 3.12;95% CI,1.70-5.72)。在调整 HbA1c 后,这些结果基本保持不变。
在接受 RP 的糖尿病男性中,术前使用他汀类药物与更差的 BCR 风险相关,尤其是 BMI 较高的男性,但这些关联可能会因同时使用二甲双胍而减轻。如果在未来的研究中得到证实,需要研究这些关联的基础。