Impact of Metformin on the Incidence of Thrombosis in Older Adults with Polycythemia Vera or Essential Thrombocythemia and Diabetes

Individuals with myeloproliferative neoplasms (MPNs) have an increased thrombotic risk, particularly in the presence of cardiovascular comorbidities such as diabetes (DM). Metformin (MET) has been associated with a reduced incidence of MPNs; however, data on its association with thrombotic outcomes in polycythemia vera (PV) and essential thrombocythemia (ET) are limited. We conducted a retrospective study using the Surveillance, Epidemiology, and End Results-Medicare-linked database to evaluate the association between MET use and thrombotic risk in patients with MPNs and DM. We included patients with DM aged ≥66 years diagnosed with PV or ET between 2008-2019, continuously enrolled in Medicare Parts A/B/D, and followed for ≥6 months after diagnosis. Adjusted competing risk models were used to evaluate the association between MET and thrombotic risk. Among 1153 eligible patients (PV, n=528; ET, n=629), 846 (73.4%) had mild and 307 (26.6%) had severe DM. A total of 431 (37.4%) used MET. Overall, 485 (42.1%) patients experienced thrombosis after MPN diagnosis. MET use was independently associated with a reduced thrombotic risk (hazard ratio [HR]=0.78, 95% confidence interval [CI]: 0.64-0.95; p=0.02), especially among patients with severe DM (HR=0.58, 95% CI: 0.38-0.89; p=0.01), and those without prior thrombosis (HR=0.78, 95% CI: 0.62-0.97; p=0.02), but not among those with mild DM (HR=0.87, 95% CI: 0.68-1.11; p=0.27). When evaluating thrombotic event types separately, this benefit applied to arterial, but not venous thrombosis. MET use was associated with a lower thrombotic risk in older patients with PV/ET, primarily in individuals with severe DM.