Cholangiocarcinoma (CCA) is the second most common liver cancer. Diabetes is a well-known risk factor; however, treatment with metformin has been reported to be protective for several cancers, but data on CCA are still sparse and heterogeneous. We performed this meta-analysis to investigate the role of metformin as a potential protective factor for CCA. In this systematic review and meta-analysis, we searched PubMed/MEDLINE and EMBASE databases, from the date of inception to November 2022, for studies analyzing CCA rate in patients taking metformin. Twenty-nine articles were initially identified, of which four were eligible and included in our systematic review and meta-analysis, from which we estimated the relative risk (RR). The rate of CCA was lower for diabetic patients taking metformin than diabetic patients without metformin intake when comparing two highest quality studies [RR, 0.38; 95% confidence interval (CI), 0.290-0.508; P < 0.001], and three studies with similar inclusion criteria (RR, 0.34; 95% CI, 0.51-0.35; P < 0.001) without significant statistical heterogeneity among them (I2 = 29.83%, P = 0,2326 and I2 = 35.08%; P = 0.2143, respectively). Our study demonstrated a significant impact of metformin in reducing the risk of CCA by nearly 62-66% in diabetic patients taking metformin.
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