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Meta-Analysis
. 2025 May 30;61(6):1021.
doi: 10.3390/medicina61061021.

Metformin: A Dual-Role Player in Cancer Treatment and Prevention: A Comprehensive Systematic Review and Meta-Analysis

Imran Rangraze  1 , Adil Farooq Wali  2 , Mohamed El-Tanani  2 , Mohamed Anas Patni  3 , Syed Arman Rabbani  2 , Rasha Babiker  4 , Shakta Mani Satyam  5 , Yahia El-Tanani  6 , Manfredi Rizzo  1   7
Affiliations
Meta-Analysis

Metformin: A Dual-Role Player in Cancer Treatment and Prevention: A Comprehensive Systematic Review and Meta-Analysis

Imran Rangraze et al. Medicina (Kaunas). .

Abstract

Background and Objectives: Metformin is said to reduce the incidences and deaths resulting from cancer in patients suffering from type 2 diabetes mellitus, but the results have been inconsistent. Perform a systematic review and meta-analysis concentrating on the different outcomes of several cancers while taking into account the impact of metformin use. Materials and Methods: As of 15 October 2024, the literature for Medline, Embase, and Web of Science was systematically searched. ROBINS-I and the RoB 2 tool were used for assessing the risk of bias in observational studies and randomized controlled trials (RCTs), respectively. The strength of the evidence with respect to the GRADE criteria was checked. Random effects meta-analyses were conducted alongside sensitivity analyses, subgroup analyses, and meta-regressions. By utilizing funnel plots as well as Egger's test and trim-and-fill analysis, publication bias was evaluated. Results: In total, 65 studies were included in the final analyses: Metformin intake was linked to a lower risk of cancer (RR 0.72; 95% CI: 0.64-0.81, I2 = 45%). Significant reductions were observed in breast cancer (RR 0.68; 95% CI: 0.55-0.83) and colorectal cancers (RR 0.62; 95% CI: 0.51-0.76). Evidence certainty fluctuated from moderate to low, though analyses confirmed the results. Plofs funded the publication bias, but adjustment in trim-and-fill did not change the outcome significantly. Conclusions: Metformin intake seems to lower the chances of developing several types of cancers, especially breast and colorectal cancers, but the observational designs hinder determining the causal factors for observational studies. There is a need for large RCTs.

Keywords: cancer; metformin; prevention; treatment.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
PRISMA flow chart demonstrating selection of studies in this systematic review and meta-analysis.
Figure 2
Figure 2
Forest plot graph for metformin’s role in cancer risk, treatment, and prevention in breast cancer [17,23,30,42,45,49].
Figure 3
Figure 3
Forest plot for metformin role in cancer risk, treatment, and prevention in prostate cancer [18,29,37,41,53].
Figure 4
Figure 4
Forest plot graph for metformin role in cancer risk, treatment, and prevention in pancreatic cancer [10,13,39].
Figure 5
Figure 5
Funnel plot of metformin role in cancer risk, treatment and prevention. (A) All types of cancers. (B) Breast cancer. (C) Prostate cancer. (D) Pancreatic cancer. (E) Other type of cancer. Each plot displays study-level effect sizes against standard errors. The vertical blue dashed line represents the pooled effect estimate, and red dashed lines indicate the pseudo 95% confidence limits. Asymmetry in plots (A,B) may indicate small-study effects or publication bias. Panels (C–E) demonstrate more symmetric distributions.
See this image and copyright information in PMC

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