Revisiting metformin as a chemotherapy adjuvant: a systematic review and meta-analysis based on recent randomized-controlled trials
Abstract
The primary objective is to assess metformin’s impact on progression free survival (PFS), overall survival (OS), and overall response rates (ORR). Secondary objectives included chemotherapy-related toxicity, glucose metabolism, and quality of life.
A systematic review and meta-analysis were conducted following PRISMA guidelines and registered prospectively in PROSPERO. A comprehensive literature search was performed in November 2024 across PubMed, Google Scholar, Ovid MEDLINE, and ClinicalTrials.gov. Randomized controlled trials evaluating metformin as an adjunct to chemotherapy were included. The primary outcomes assessed were PFS, OS, and ORR; secondary outcomes included chemotherapy-related side effects, glucose metabolism, and quality of life. Data extraction and quality assessment were performed using standardized tools, and statistical analyses were conducted using RevMan 5.4 Heterogeneity was assessed using the
I²
statistic, and a random-effects model was applied when necessary.
Nineteen RCTs involving 3,502 participants were included. Subgroup analyses demonstrated a significant OS benefit when metformin (1500 mg/day) was combined with platinum-based chemotherapy (HR = 0.61, 95% CI 0.46–0.81;
p
= 0.0006). Metformin also significantly improved ORR in patients with breast cancer (OR = 1.86, 95% CI 1.19–2.92;
p
= 0.007) and in studies using a 500 mg/day dose (OR = 3.39, 95% CI 1.37–8.39;
p
= 0.008). Overall, metformin significantly improved ORR (OR = 1.59, 95% CI…
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: 3,502 participants or records.
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