Impact of metformin use on the outcomes of newly diagnosed diffuse large B‐cell lymphoma and follicular lymphoma

Abstract

Summary The diabetes mellitus (DM) drug metformin targets mechanistic/mammalian target of rapamycin and inhibits lymphoma growth in vitro. We investigated whether metformin affected outcomes of newly diagnosed diffuse large B‐cell (DLBCL, n = 869) and follicular lymphoma (FL, n = 895) patients enrolled in the Mayo component of the Molecular Epidemiology Resource cohort study between 2002 and 2015. Hazard ratios (HR) and 95% confidence intervals (CIs) adjusted for age, sex, body mass index, prognostic index and treatment were used to estimate the association of metformin exposure (No DM/No metformin; DM/No metformin; DM/Metformin) with event‐free (EFS), lymphoma‐specific (LSS) and overall (OS) survival. Compared to No DM/No metformin DLBCL patients, there was no association of DM/Metformin (n = 48; HR = 1·05, 95% CI 0·59–1·89) or DM/No metformin(n = 54; HR = 1·41, 95% CI 0·88–2·26) with EFS; results were similar for LSS and OS. Compared to No DM/No metformin FL patients, there was no association of DM/Metformin (n = 37; HR = 1·16, 95% CI 0·71–1·89) or DM/No metformin (n = 19; HR = 1·16, 95% CI 0·66–2·04) with EFS; results were similar for LSS. However, DM/Metformin was associated with inferior OS (HR = 2·17; 95% CI 1·19–3·95) compared to No DM/No metformin. In conclusion, we found no evidence that metformin use was associated with improved outcomes in newly diagnosed DLBCL and FL.

Statin and cyclooxygenase‐2 inhibitors improve survival in newly diagnosed diffuse large B‐cell lymphoma: a large population‐based study of 4913 subjects

“…However, in a retrospective review of 213 patients, 31 on metformin at presentation, no difference in outcome was identified 6 . A recent publication 25 identified no survival advantage in patients with newly diagnosed DLBCL or FL exposed to metformin at time of diagnosis. In our present cohort, 16% of the patients received metformin with no association between OS and any metformin exposure, or any time‐varying exposure impact.…”

Metformin and Cancer, an Ambiguanidous Relationship

“…In a population-based case-control study and two large, retrospective analyses, there were no significant correlations between metformin use and disease progression or survival in patients with non-Hodgkin lymphoma (NHL) [ 75 , 76 , 77 ]. However, in a Taiwanese study using a database of over 600,000 newly diagnosed DM patients enrolled in the National Health Insurance database, metformin initiators consistently had a lower risk of NHL [ 78 ].…”

Second malignant neoplasms in lymphomas, secondary lymphomas and lymphomas in metabolic disorders/diseases

“…Although some reports indicated that metformin might improve outcomes of lymphoma patients, the results from the previous studies showed inconsistent. In a cohort study of newly diagnosed DLBCL (n = 869) and FL (n = 895) patients enrolled in the Mayo component of the Molecular Epidemiology Resource cohort study between 2002 and 2015, the results showed that use of metformin was not associated with improved outcomes in newly diagnosed DLBCL and FL [ 114 ]. Metformin has been repeatedly shown to regulate lipid metabolism, not only via its antidiabetic effect but also through the activation of adenosine monophosphate kinase (AMPK) which mediates the regulations of peroxisomal proliferator-activated receptor α (PPARα) and PPARγ [ 115 – 117 ].…”