Efficacy of metformin therapy in patients with cancer: a meta-analysis of 22 randomised controlled trials

Jie Wen; Zhenjie Yi; Yuyao Chen; Jing Huang; Xueyi Mao; Liyang Zhang; Yu Zeng; Quan Cheng; Wenrui Ye; Zhixiong Liu; Fangkun Liu; Jingfang Liu

doi:10.1186/s12916-022-02599-4

Efficacy of metformin therapy in patients with cancer: a meta-analysis of 22 randomised controlled trials

BMC Med. 2022 Oct 24;20(1):402. doi: 10.1186/s12916-022-02599-4.

Authors

Jie Wen^#^{1

2}, Zhenjie Yi^#^{1

2}, Yuyao Chen³, Jing Huang⁴, Xueyi Mao¹, Liyang Zhang^{1

5}, Yu Zeng^{1

2}, Quan Cheng^{1

5}, Wenrui Ye^{1

2}, Zhixiong Liu^{1

2}, Fangkun Liu^#^{6

7}, Jingfang Liu^#^{8

9}

Affiliations

¹ Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, Hunan, China.
² Hypothalamic Pituitary Research Center, Xiangya Hospital, Central South University, Changsha, Hunan, China.
³ Department of Epidemiology and Health Statistics, Xiangya School of Public Health, Central South University, Changsha, Hunan, China.
⁴ National Clinical Research Center for Mental Disorders and Department of Psychiatry, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China.
⁵ National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, China.
⁶ Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, Hunan, China. liufangkun@csu.edu.cn.
⁷ Hypothalamic Pituitary Research Center, Xiangya Hospital, Central South University, Changsha, Hunan, China. liufangkun@csu.edu.cn.
⁸ Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, Hunan, China. jinfang_liu@csu.edu.cn.
⁹ Hypothalamic Pituitary Research Center, Xiangya Hospital, Central South University, Changsha, Hunan, China. jinfang_liu@csu.edu.cn.

^# Contributed equally.

Abstract

Background: 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).

Methods: 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.

Results: 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, 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.

Conclusion: 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.

Systematic review registration: PROSPERO registration number CRD42022324672.

Keywords: Cancer; Cancer-related mortality; Meta-analysis; Metformin; RCTs.

Publication types

Meta-Analysis
Research Support, Non-U.S. Gov't

MeSH terms

Adult
Combined Modality Therapy
Humans
Metformin* / therapeutic use
Neoplasms* / drug therapy
Randomized Controlled Trials as Topic

Substances

Metformin