Adults who have type 2 diabetes often use metformin to balance their blood sugar. This safe and inexpensive drug is accepted as the first treatment for this condition. However, there is also a growing interest in the potential of metformin to prevent or treat common cancers like breast, prostate and colon. Some laboratory data also suggest metformin may have activity against lymphoma, or cancer of the lymph nodes, and associated cancers, which can appear in blood (leukemia) or bone (multiple myeloma). However, little is known on the risk of these cancers in people with diabetes who use metformin. We will therefore study a large population of diabetics who use medications to treat their disease. We will compare the number of new cases of lymphoma and leukemia occurring in users of metformin with those in non-users. We hope to give a clear answer whether clinical trials are needed to examine metformin for this indication.
The objective of this study is to examine the risk of lymphoid malignancies with the use of metformin in patients with type 2 diabetes. We will assemble a cohort of patients newly-treated with non-insulin antidiabetic medications between 1998 and 2014 using the Clinical Practice Research Datalink (CPRD) with linkage to the Hospital Episode Statistics (HES), Index of Multiple Deprivation and the Office for National Statistics (ONS). Cohort entry will be defined by the first-ever prescription of an antidiabetic in CPRD. Primary exposure will be defined in a time-dependent fashion as the use of metformin lagged by 1 year, and the reference group will be no use of metformin. We will define the primary outcome as the first hospitalization with a diagnosis of non-Hodgkin’s lymphoma (NHL), Hodgkin’s lymphoma (HL), multiple myeloma (MM), chronic lymphoid leukemia (CLL), or acute lymphoblastic leukemia (ALL), identified in HES by international classification of diseases-10 (ICD-10) codes. Time-dependent Cox models will be used to assess the hazard ratio for the composite of lymphoid malignancies associated with the use of metformin, compared with no use. Secondary analyses will include duration- and dose-response, as well as the outcome stratified by specific malignancies.
Samy Suissa - Chief Investigator - Sir Mortimer B Davis Jewish General Hospital
Laurent Azoulay - Corresponding Applicant - McGill University
Adi Klil-Drori - Collaborator - Sir Mortimer B Davis Jewish General Hospital
Hui Yin - Collaborator - Sir Mortimer B Davis Jewish General Hospital
Michael Pollak - Collaborator - Sir Mortimer B Davis Jewish General Hospital
HES Admitted Patient Care;ONS Death Registration Data;Patient Level Index of Multiple Deprivation