Abstract
BackgroundMetformin, an insulin-sensitizer, may correct several physiologic abnormalities owing to insulin resistance in patients with type 2 diabetes mellitus (DM). The effects of metformin on venous thrombosis in patient with type 2 DM have not been reported. Our study strived to explore the relationship of metformin therapy and the subsequent development of deep vein thrombosis (DVT) using a nationwide, population-based database.MethodsFrom 1997 to 2003, we identified a study cohort consisting of patients with type 2 DM using metformin 7154 cases in the National Health Insurance Research Database. A control cohort without metformin, matched for age, sex, comorbidities, and medications was selected for comparison.ResultsOf the 14945 patients (7167 patients with metformin vs. 7778 control), 60 (0.40%) patients developed DVT during a mean follow-up period of 3.74 years, including 16 (0.21%) from the cohort with metformin and 44 (0.56%) from the control group. Subjects with metformin experienced a 0.427 fold (95% confidence interval 0.240-0.758; P = 0.004) changes of risk reduction in development of DVT, which was independent of age, sex and co-morbidities. Kaplan-Meier analysis also revealed metformin therapy is associated with lower occurrence of DVT (log-rank test, P = 0.001).ConclusionsMetformin may have protective effect in patients with type 2 DM for DVT.
Highlights
Metformin, an insulin-sensitizer, may correct several physiologic abnormalities owing to insulin resistance in patients with type 2 diabetes mellitus (DM)
We hypothesized that metformin may reduce the development of venous thrombosis in patient with type 2 diabetes
We conducted this nonrandomized, pair-matched cohort study to investigate the relationship between metformin therapy and the subsequent development of deep venous thrombosis among patients with type 2 diabetes mellitus
Summary
Database The National Health Insurance program in Taiwan has been operating since 1995 and has enrolled most the inhabitants of Taiwan (23,074,487 beneficiaries out of 23,162,123 inhabitants at the end of 2010). It is one of the largest nationwide population-based databases in the world, with more than 1000 scientific articles published using its data [7] In this cohort dataset, each patient’s original identification number has been encrypted to protect privacy. To investigate the causal relationship between metformin use and deep venous thrombosis (DVT) occurrence, in both groups, subjects with pre-existing DVT (ICD-9-CM codes 453.0-453.9) before enrollment were excluded from this study. Deep vein thrombosis event measurement The end point of the study was defined as occurrence of DVT (ICD-9-CM codes 453.0-453.9) In this database, the ICD codes of DVT and the drug code of metformin did not change throughout the whole follow-up period (1997–2003), assuring the consistency of the disease and medication registry. Statistical significance was inferred at a 2-sided P value of
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