van Hattum Jons W, Remmelink Marinka J, Nuijens Sieb T, de Ruiter Ben Max, Hooijer Gerrit K J, Oddens Jorg R, Savci-Heijink C Dilara, Mathot Ron, Witjes J Alfred, Pollak Michael N, de Reijke Theo M, Molenaar Remco J, Wilmink Hanneke W
Department of Urology, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.
Cancer Center Amsterdam, Cancer Treatment and Quality of Life, Amsterdam, The Netherlands.
BJU Int. 2025 Oct;136(4):738-746. doi: 10.1111/bju.16767. Epub 2025 May 22.
To evaluate the effect of metformin on non-muscle-invasive bladder cancer (NMIBC) marker lesions.
A phase II, open-label, multicentre, marker lesion trial using oral metformin in patients with primary or recurrent, multiple, low-grade Ta-T1 NMIBC was conducted. After transurethral resection for histological confirmation, leaving one tumour as a marker lesion, 11 patients were treated with oral metformin up to 3000 mg per day for 3 months. Reported outcomes included response of the marker lesion, safety of metformin, quality of life and pharmacological and immunohistochemical examinations of the mechanism of action of metformin.
One complete response and one partial response were observed. In the other nine patients, the marker lesion remained, while five of these patients also developed new Ta low-grade lesions. Diarrhoea grade ≤ 2 was the most common adverse event (AE), observed in nine out of 11 patients. No serious AEs related to study treatment occurred. Metformin concentrations in the urine were significantly higher than metformin levels in the blood. Immunohistochemical analysis before and after treatment showed no difference in expression of markers associated with the mechanism of metformin.
We did not find conclusive evidence for the hypothesis of an antitumour effect of metformin in bladder cancer.
评估二甲双胍对非肌层浸润性膀胱癌（NMIBC）标记性病变的影响。
开展一项II期、开放标签、多中心的标记性病变试验，对原发性或复发性、多发性、低级别Ta-T1期NMIBC患者使用口服二甲双胍进行治疗。经尿道切除术后进行组织学确认，保留一个肿瘤作为标记性病变，11例患者接受口服二甲双胍治疗，每日剂量高达3000毫克，持续3个月。报告的结果包括标记性病变的反应、二甲双胍的安全性、生活质量以及二甲双胍作用机制的药理学和免疫组化检查。
观察到1例完全缓解和1例部分缓解。在其他9例患者中，标记性病变依然存在，其中5例患者还出现了新的Ta低级别病变。腹泻≤2级是最常见的不良事件（AE），11例患者中有9例出现。未发生与研究治疗相关的严重不良事件。尿液中的二甲双胍浓度显著高于血液中的二甲双胍水平。治疗前后的免疫组化分析显示，与二甲双胍作用机制相关的标志物表达无差异。
我们未找到确凿证据支持二甲双胍对膀胱癌具有抗肿瘤作用这一假说。
