• Jie Wen, Zhenjie Yi, Yuyao Chen, Jing Huang, Xueyi Mao, Liyang Zhang, Yu Zeng, Quan Cheng, Wenrui Ye, Zhixiong Liu, Fangkun Liu, and Jingfang Liu.
• Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, Hunan, China.
• Bmc Med. 2022 Oct 24; 20 (1): 402.

BackgroundTo investigate whether metformin monotherapy or adjunctive therapy improves the prognosis in patients with any type of cancer compared to non-metformin users (age ≥18).MethodsDatabases (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.ResultsOf 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, I2 = 50%) and OS (HR 0.98, 95% CI 0.86-1.13, I2 = 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.ConclusionMetformin 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.Systematic Review RegistrationPROSPERO registration number CRD42022324672.© 2022. The Author(s).

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