Past use of metformin is associated with increased risk of myelodysplastic syndrome development in diabetes mellitus patients: a cross-sectional study of 54,869 patients.

Abstract

Background: Myelodysplastic Syndrome (MDS) is a devastating hematologic malignancy associated with advanced age. Diabetes Mellitus (DM) is one of the most common morbidities worldwide, with metformin serving as the first line therapy for several decades. However, the potential association between previous metformin use and the risk of developing MDS remains uncertain.

Methods: This cross-sectional study addressed the possible association between prior metformin use in DM patients and the subsequent development of MDS.

Results: Data from 54,869 DM patients was retrieved from their medical records from a tertiary medical center. Of these, 20,318 patients had been exposed at some point in time to metformin, with 133 (0.7%) subsequently developing MDS. In contrast, among 34,551 DM patients with no prior exposure to metformin, only 154 (0.4%) developed MDS later in life. The Odds Ratio (OR) for MDS development amongst metformin users compared to the entire study population was 1.48 (95% CI 1.17-1.86; p = 0.001). A multivariate analysis adjusting for gender, age, congestive heart failure and chronic kidney disease, past exposure to metformin remained an independent risk factor for MDS development (OR = 1.6, 95% CI 1.26-2.03; p < 0.001).

Conclusion: Previous exposure to metformin amongst DM patients is associated with an increased risk for MDS development later in life. This is a preliminary, cross-sectional study that show that larger studies in variable MDS patient populations are warranted.