Metformin Is Not Associated with Incidence Risk of Non-Hodgkin Lymphomas among Diabetic Patients

Abstract

Several epidemiological studies have shown a positive association between diabetes and increased risk of non-Hodgkin lymphoma (NHL), but the effect of diabetic treatment drugs such as metformin on the risk is unknown. We conducted a population-based nested case-control study involving 878 NHL cases and 4,364 controls diagnosed with diabetes. Use of metformin and other medications before diagnosis and medical condition histories were assessed using administrative databases. We used conditional logistic regression models to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for use of metformin, adjusting for confounders. Risk of total NHLs is not associated with ever use of metformin (OR, 0.93; 95% CI, 0.79-1.10) among diabetic patients. NHL subtypes were also not associated with metformin use. Metformin use is not associated with overall or subtype NHL risk among diabetic patients. NHLs are etiologically heterogeneous and larger scale studies are warranted to test the potential effect of metformin by NHL subtype. .

Diabetes, metformin use and risk of non‐Hodgkin's lymphoma in postmenopausal women: A prospective cohort analysis in the Women's Health Initiative

“…However, our findings indicated that women who were treated with oral antidiabetic agents, especially metformin, had an increased risk of DLBCL compared to women without treatments or nondiabetics. Evidence from several studies has suggested that oral antidiabetic drug use, especially metformin, is associated with decreased risks for many solid tumors, including pancreatic cancer, 42 breast cancer 43 and prostate cancer, 44 while this benefit was not observed for DLBCL 23,45,46 . Although inconsistent findings have been reported, previous results might be attributed to the failure to consider residual confounding factors, the small number of cases, possible recall bias in the case‐control studies, quantification of the duration of exposure to T2DM, latency time window and immortal time bias due to time‐fixed analyses that misclassify unexposed person‐time as exposed 23,47 .…”

“…Evidence from several studies has suggested that oral antidiabetic drug use, especially metformin, is associated with decreased risks for many solid tumors, including pancreatic cancer, 42 breast cancer 43 and prostate cancer, 44 while this benefit was not observed for DLBCL 23,45,46 . Although inconsistent findings have been reported, previous results might be attributed to the failure to consider residual confounding factors, the small number of cases, possible recall bias in the case‐control studies, quantification of the duration of exposure to T2DM, latency time window and immortal time bias due to time‐fixed analyses that misclassify unexposed person‐time as exposed 23,47 . A NHL‐related study reported positive associations between metformin and event‐free survival (EFS) and overall survival (OS) of DLBCL among T2DM patients 46 .…”

“…23,45,46 Although inconsistent findings have been reported, previous results might be attributed to the failure to consider residual confounding factors, the small number of cases, possible recall bias in the case-control studies, quantification of the duration of exposure to T2DM, latency time window and immortal time bias due to time-fixed analyses that misclassify unexposed person-time as exposed. 23,47 A NHL-related study reported positive associations between metformin and event-free survival (EFS) and overall survival (OS) of DLBCL among T2DM patients. 46 In line with the previous findings, we also found a significant increase in the risk of DLBCL among metformin users based on the current large cohort.…”

“…21,22 Studies suggest that metformin can affect most sites of impaired insulin secretion and insulin resistance (IR), and many metabolic alterations brought about by IR can be improved by metformin. 21 However, there have been few studies of the associations of antidiabetic treatment with risks of NHL and its histological subtypes, 23 particularly for postmenopausal women.…”

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 ].…”