Background: Diffuse large B-cell lymphoma (DLBCL) is the leading form of adult non-Hodgkin lymphoma (NHL), accounting for 4–5% of new cancer diagnoses and 3–4% of cancer-related mortalities. Preliminary studies on the addition of metformin to chemotherapy have resulted in higher survival and response rates, but the results found still vary. Since no meta-analysis has been published examining this topic, our study investigates the efficacy of metformin as an adjuvant in DLBCL by measuring Overall Survival (OS), Event-Free Survival (EFS), and Objective Response Rate (ORR). Material and Methods: Literature retrieval included searches in four main databases, including PubMed, Scopus, Cochrane, and ClinicalTrials.gov, from all publication years. The search keywords included “Metformin,” “DLBCL,” “Adjuvant therapy,” and “Diabetes Mellitus”. PRISMA checklist was used to select articles to ensure a comprehensive review. The quality of each article was critically reviewed using the Cochrane RoB 2 tools for RCTs or ROBINS-I for non-randomised studies. Results: From the search results, 7 studies were identified (n = 1344). OS and EFS were found to be significantly better in the metformin group compared to the control group, with a hazard ratio (HR) of 0.54 0.34–0.87 and 0.54 0.36–0.82, respectively; while ORR was found to be non-significant (RR: 1.16 0.98–1.38). Subgroup analysis for studies with diabetic populations showed similar significant effects on OS and EFS, with HR of 0.54 0.33–0.88 and 0.56 0.40–0.77, respectively. Meta-regression results indicate greater therapeutic effect (lower OS and EFS hazard ratio) in lower risk patients (International Prognostic Index (IPI) score 0–2). Conclusion: Metformin as adjuvant therapy in DLBCL patients has demonstrated a trend in reducing mortality and disease progression, more effectively in lower-risk patients (IPI score 0–2). To further elaborate on the beneficial effects of metformin, a prospective, randomised, double-blinded study with a larger population is warranted, specifically targeting the low-risk DLBCL patients.
Ramadhan et al. (2026) studied this question.