Neoadjuvant metformin on clinical and pathological response in non-diabetic patients with non-metastatic breast cancer: an updated systematic review and meta-analysis
Abstract
Introduction: Metformin has been explored as an anticancer agent in breast cancer, but randomized trial evidence remains inconsistent. This updated review evaluated neoadjuvant metformin's effect on response outcomes in non-diabetic patients with non-metastatic breast cancer.
Methods: A systematic review and meta-analysis were conducted (PROSPERO: CRD420251039988). PubMed, Web of Science, ClinicalTrials.gov, and ICTRP were searched until April 2025. Randomized-controlled trials comparing neoadjuvant metformin plus standard of care (SOC) versus SOC alone in non-diabetic patients with stage I-III breast cancer were included. Primary outcomes were pathological and clinical complete response (pCR/cCR); secondary outcomes were overall response and pathological response (oRR/oPR), with breast-conserving surgery (BCS) evaluated as a tertiary outcome. Risk ratios (RRs) with 95% confidence intervals (CIs) were pooled using random-effects models. Post-hoc meta-regression and subgroup analyses were also performed.
Results: Fifteen trials, including 1,125 patients, were analyzed. Metformin was not significantly associated with improvements in pCR (RR 1.17, 95% CI 0.97-1.40), cCR (RR 1.53, 95% CI 0.87-2.70), oRR (RR 1.23, 95% CI 0.89-1.69), oPR (RR 1.21, 95% CI 0.96-1.52), or BCS (RR 1.10, 95% CI 0.90-1.35). Exploratory subgroup analysis suggested increased pCR in HER2 + disease (RR 1.22, 95% CI 1.01-1.49). Higher study-level body mass index (BMI) was associated with improved response…
How strong is the evidence?
Evidence Hub reads this as a meta-analysis, done in people. Its evidence level is 1 of 5 (Highest · pooled evidence). Pooled evidence from several studies sits at the top of the evidence pyramid. Reported size: 1,125 participants or records.
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