Revisiting metformin as a chemotherapy adjuvant: a systematic review and meta-analysis based on recent randomized-controlled trials.
6 affiliations
- 1Faculty of Medicine and Surgery, Batterjee Medical College, Jeddah, Saudi Arabia.
- 2College of Medicine, Alfaisal University, Riyadh, Saudi Arabia.
- 3College of Medicine, King Saud Bin Abdulaziz University for Health Sciences, Jeddah, Saudi Arabia.
- 4King Abdullah International Medical Research Center, Jeddah, Saudi Arabia.
- 5Department of Internal Medicine, Division of Endocrinology, Ministry of the National Guard-Health Affairs, Jeddah, Saudi Arabia.
- 6Department of Clinical Pharmacology and Toxicology, College of Medicine, Umm Al-Qura University, Makkah, Saudi Arabia.
Abstract
Objective
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.Methods
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.Results
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 1.02-2.46; p = 0.04). However, no significant improvements were observed in overall PFS (HR = 1.08, 95% CI 0.96-1.22; p = 0.19) or OS (HR = 1.08, 95% CI 0.90-1.30; p = 0.41). Grade ≥3 adverse events were comparable between groups (OR = 1.10, 95% CI 0.66-1.84; p = 0.72).Conclusion
Adjunctive metformin did not improve overall or PFS but was associated with a higher ORR, driven by increased complete responses, without increasing high-grade toxicity. A survival benefit was observed in exploratory subgroup analyses at a 1500 mg/day dose in platinum-based chemotherapy, warranting prospective trials to clarify these findings.
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BibTeX
@article{saddiq2026revisiting,
title = {{Revisiting metformin as a chemotherapy adjuvant: a systematic review and meta-analysis based on recent randomized-controlled trials.}},
author = {Bushra Wadi Bin Saddiq and Ahmed Salah Morad and Tanveer Nidal Khan and Joud Jamal Alshowaikhat and Jorie Nasser Alsharari and Renad Omar Bajri and Meral Jehad AlZayer and Saaid Mounzer Mouazen and Mohammed Abdulhameed Abutaleb and Suhaib Radi and Hassan Alwafi},
journal = {Frontiers in oncology},
year = {2026},
month = sep,
doi = {10.3389/fonc.2026.1888506},
url = {https://europepmc.org/article/MED/42840671},
note = {CC BY},
}
RIS
TY - JOUR
TI - Revisiting metformin as a chemotherapy adjuvant: a systematic review and meta-analysis based on recent randomized-controlled trials.
AU - Bushra Wadi Bin Saddiq
AU - Ahmed Salah Morad
AU - Tanveer Nidal Khan
AU - Joud Jamal Alshowaikhat
AU - Jorie Nasser Alsharari
AU - Renad Omar Bajri
AU - Meral Jehad AlZayer
AU - Saaid Mounzer Mouazen
AU - Mohammed Abdulhameed Abutaleb
AU - Suhaib Radi
AU - Hassan Alwafi
PY - 2026
DA - 2026/09/09
JO - Frontiers in oncology
DO - 10.3389/fonc.2026.1888506
UR - https://europepmc.org/article/MED/42840671
AB - Objective 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.Methods 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.Results 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 1.02-2.46; p = 0.04). However, no significant improvements were observed in overall PFS (HR = 1.08, 95% CI 0.96-1.22; p = 0.19) or OS (HR = 1.08, 95% CI 0.90-1.30; p = 0.41). Grade ≥3 adverse events were comparable between groups (OR = 1.10, 95% CI 0.66-1.84; p = 0.72).Conclusion Adjunctive metformin did not improve overall or PFS but was associated with a higher ORR, driven by increased complete responses, without increasing high-grade toxicity. A survival benefit was observed in exploratory subgroup analyses at a 1500 mg/day dose in platinum-based chemotherapy, warranting prospective trials to clarify these findings.
SN - 2234-943X
ER -