The association between metformin administration and non-Hodgkin lymphoma; a systematic review and meta-analysis of cohort and case-control studies

Introduction: Metformin, a blood sugar-lowering agent, has the potential to be an anti-cancer agent. However, its role in lymphoma remains uncertain. Objectives: This study sought to examine the correlation between the utilization of metformin and non-Hodgkin lymphoma through the application of a systematic review and meta-analysis methodology. Materials and Methods: This investigation was carried out in the form of a methodical examination and meta-analysis in accordance with the PRISMA guidelines. Databases such as Scopus, PubMed, Web of Science, Cochrane, and the Google Scholar search engine were thoroughly explored without any temporal limitations until September 20, 2023. The data was analyzed utilizing the STATA 14 software, and the level of significance for the tests was established at P<0.05. Results: The results, obtained by combining six observational studies (five cohort studies and one case-control study) with a total sample size of 2 330 787 individuals, showed that the odds ratio (OR) for the association between metformin use and non-Hodgkin lymphoma in all studies was 0.91 (95% CI: 0.78, 1.07). In cohort studies, the OR was 0.91 (95% CI: 0.74, 1.11), and in the case-control study, it was 0.93 (95% CI: 0.79, 1.10). None of these relationships were statistically significant. The odds ratio between metformin uses and chronic lymphocytic leukemia/small lymphocytic leukemia was 0.93 (95% CI: 0.71, 1.21), and the odds ratio between metformin use and diffuse large B-cell lymphoma was 1.06 (95% CI: 0.61, 1.83), both of which were not statistically significant. Conclusion: This investigation’s findings indicated no statistically noteworthy correlation exists between the utilization of metformin and the probability of contracting non-Hodgkin lymphoma, chronic lymphocytic leukemia/small lymphocytic leukemia, and diffuse large B-cell lymphoma. Registration: This study was conducted following the PRISMA checklist. Its protocol was registered on the PROSPERO (CRD42023469100) and Research Registry (UIN: reviewregistry1721) websites.