Abstract
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.