Background:

Classical myeloproliferative neoplasms (MPNs), including polycythemia vera, essential thrombocythemia, and myelofibrosis, are associated with substantial cardiovascular and thrombotic morbidity, frequent hospitalization, and premature mortality. Type 2 diabetes and obesity are common comorbidities in this population; however, adjunctive strategies to reduce nonmalignant morbidity remain limited. We evaluated whether exposure to glucagon-like peptide-1 receptor agonists (GLP-1RAs) was associated with improved clinical outcomes among adults with classical MPNs and type 2 diabetes and/or obesity.

Methods:

We performed a retrospective propensity score-matched analysis using the TriNetX Global Collaborative Network. Adults aged 18-90 years with classical MPNs and diabetes mellitus and/or obesity were identified. Patients exposed to GLP-1RAs were compared with matched patients receiving non-GLP-1RA antidiabetic therapy. Outcomes were assessed from 30 days to 5 years after the index date. After matching for demographics, comorbidities, laboratory variables, medication exposures, and selected oncologic characteristics, 1,837 patients remained in each cohort.

Results:

GLP-1RA exposure was associated with significantly lower risks of all-cause mortality (1.0% vs 4.3%; HR, 0.23; 95% CI, 0.14-0.39; p<0.001), venous thromboembolism (1.9% vs 3.0%; HR, 0.59; 95% CI, 0.38-0.92; p=0.020), hospitalization (5.4% vs 10.4%; HR, 0.51; 95% CI, 0.39-0.67; p<0.001), ischemic heart disease (4.0% vs 7.7%; HR, 0.49; 95% CI, 0.36-0.67; p<0.001), and heart failure (1.6% vs 4.3%; HR, 0.37; 95% CI, 0.24-0.58; p<0.001). The risk of cerebral infarction was numerically lower in the GLP-1RA cohort but did not reach statistical significance (0.6% vs 1.1%; HR, 0.55; 95% CI, 0.26-1.15; p=0.108). Median follow-up after matching was 541 days in the GLP-1RA cohort and 442 days in the comparator cohort.

Conclusions:

In this global propensity score-matched analysis, GLP-1RA exposure among adults with classical MPNs and diabetes and/or obesity was associated with lower risks of death, venous thromboembolism, hospitalization, and major cardiovascular events. These findings support GLP-1RAs as a promising repurposing candidate to reduce nonmalignant morbidity in classical MPNs and warrant prospective studies incorporating biomarker- and thrombosis-focused endpoints.