Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, Hunan, China.
Hypothalamic Pituitary Research Center, Xiangya Hospital, Central South University, Changsha, Hunan, China.
BMC Med. 2022 Oct 24;20(1):402. doi: 10.1186/s12916-022-02599-4.
To investigate whether metformin monotherapy or adjunctive therapy improves the prognosis in patients with any type of cancer compared to non-metformin users (age ≥18).
Databases (Medline, Embase, and the Cochrane Central Register of Controlled Trials) and clinical trial registries ( ClinicalTrials.gov ; the World Health Organization International Clinical Trials Registry Platform) were screened for randomized, controlled trials (RCT) reporting at least progression-free survival (PFS) and/or overall survival (OS). Main outcome measures included hazard ratios (HR), and combined HRs and 95% confidence intervals (CI) were calculated using random-effects models.
Of the 8419 records screened, 22 RCTs comprising 5943 participants were included. Pooled HRs were not statistically significant in both PFS (HR 0.97, 95% CI 0.82-1.15, I = 50%) and OS (HR 0.98, 95% CI 0.86-1.13, I = 33%) for patients with cancer between the metformin and control groups. Subgroup analyses demonstrated that metformin treatment was associated with a marginally significant improvement in PFS in reproductive system cancers (HR 0.86, 95% CI 0.74-1.00) and a significantly worse PFS in digestive system cancers (HR 1.45, 95% CI 1.03-2.04). The PFS or OS was observed consistently across maintenance dose, diabetes exclusion, median follow-up, risk of bias, and combined antitumoral therapies.
Metformin treatment was not associated with cancer-related mortality in adults compared with placebo or no treatment. However, metformin implied beneficial effects in the PFS of the patients with reproductive system cancers but was related to a worse PFS in digestive system cancers.
PROSPERO registration number CRD42022324672.
本研究旨在探讨与非二甲双胍使用者（年龄≥18 岁）相比，二甲双胍单药或联合治疗是否能改善任何类型癌症患者的预后。
通过筛选 Medline、Embase 和 Cochrane 对照试验中心注册库等数据库以及临床试验注册处（ClinicalTrials.gov；世界卫生组织国际临床试验注册平台），以获取至少报告无进展生存期（PFS）和/或总生存期（OS）的随机对照试验（RCT）。主要观察指标包括风险比（HR），采用随机效应模型计算合并 HR 及其 95%置信区间（CI）。
在筛选的 8419 条记录中，纳入了 22 项包含 5943 名参与者的 RCT。在癌症患者的二甲双胍组和对照组之间，PFS（HR 0.97，95%CI 0.82-1.15，I=50%）和 OS（HR 0.98，95%CI 0.86-1.13，I=33%）的合并 HR 均无统计学意义。亚组分析表明，与对照组相比，二甲双胍治疗与生殖系统癌症的 PFS 略有改善（HR 0.86，95%CI 0.74-1.00），与消化系统癌症的 PFS 显著恶化（HR 1.45，95%CI 1.03-2.04）相关。在维持剂量、排除糖尿病、中位随访时间、偏倚风险和联合抗肿瘤治疗方面，PFS 或 OS 是一致的。
与安慰剂或不治疗相比，二甲双胍治疗与成年人的癌症相关死亡率无关。然而，二甲双胍对生殖系统癌症患者的 PFS 有有益影响，但与消化系统癌症的 PFS 恶化有关。
PROSPERO 注册号 CRD42022324672。
