GLP-1 Agonists Show Therapeutic Benefits in Polycythemia Vera Population

“Every parameter, both for primary and secondary outcomes, was statistically significantly decreased in patients who were taking a GLP-1a vs those who were not,” stated presenting author Asfand Yar Cheema, MD.

Statistically significant reductions in all-cause mortality, progression to myelofibrosis, and venous thromboembolism (VTE) occurred among patients with polycythemia vera (PV) who received glucagon-like peptide-1 receptor agonists (GLP-1a), according to data from a propensity-matched analysis presented at the 2025 Society of Hematologic Oncology Annual Meeting.

Additionally, the use of GLP-1a conferred a low incidence of hospitalization, intensive care unit (ICU) admission, acute kidney injury (AKI), and ischemic stroke or transient ischemic attack (TIA) in this patient population.

“Every parameter, both for primary and secondary outcomes, was statistically significantly decreased in patients who were taking a GLP-1a vs those who were not,” presenting author Asfand Yar Cheema, MD, stated in the presentation.

Cheema is a hematology/oncology resident physician at the Cleveland Clinic, in Columbus, Ohio.

Among patients with PV, those receiving GLP-1a therapy experienced lower rates of several adverse outcomes compared with non-users. AKI occurred in 11.72% of users of GLP-1a vs 16.37% of non-users. The rate of progression to myelofibrosis was 1.70% in GLP-1a users compared with 3.06% in non-users.

VTE affected 8.33% of patients who received GLP-1a vs 11.41% in non-users, and ICU admissions occurred in 7.45% of users of GLP-1a vs 13.35% of non-users; the rates of all-cause hospitalizations were 44.82% vs 54.14%, respectively. Mortality occurred in 4.47% of GLP-1a users compared with 8.72% non-users. Rates of ischemic stroke or TIA were 7.45% vs 8.84%.

PV Overview and Emerging Role of GLP-1 Agonists

PV is a chronic myeloproliferative neoplasm, with approximately 95% of patients harboring the JAK2 V617F mutation. Key complications include venous thromboembolism, which occur in approximately 34% to 41% of patients, progression to myelofibrosis in 10% to 15%, and leukemic transformation in approximately 3% to 4%.

GLP-1a, primarily used for glycemic control and weight management, have emerging evidence suggesting they may reduce the risk of myelodysplastic syndromes and myeloproliferative neoplasms in patients with type 2 diabetes mellitus or autoimmune disorders. Preclinical studies indicate GLP-1a possess antineoplastic and anti-inflammatory activity, producing cytostatic effects and modulation of the JAK/STAT pathway.

“GLP-1 receptor agonists increase cyclic AMP activity, inhibit ERK pathways, and modulate MAPK downward…ultimately increasing apoptosis and decreasing cellular proliferation in neoplastic cells,” Cheema emphasized in the presentation.

Building on the preclinical rationale, investigators aimed to evaluate the association between GLP-1a therapy and key clinical outcomes in patients with PV using a large global database. The analysis focused on primary outcomes of all-cause mortality, progression to myelofibrosis, and VTE. Secondary outcomes included all-cause hospitalizations, ICU admissions, AKI, and TIA.

The study was conducted as a retrospective cohort analysis using data from the TriNetX Analytics Network during 2010 to 2022, encompassing 147 healthcare organizations. The population included 5,291 patients with PV receiving GLP-1a and 79,027 patients who were not using these therapies.

Patients were followed for 3 years from the index event, defined as the time of PV diagnosis while receiving GLP-1a therapy. The mean duration of GLP-1 receptor agonist therapy among patients was approximately 298 days, with a standard deviation of approximately 162 days.

Study Limitations and Future Research Directions

Overall, investigators emphasized that the use of GLP-1 receptor agonists led to a therapeutic benefit among patients. Additionally, therapy was linked to reduced healthcare utilization, including fewer hospitalizations and ICU admissions, as well as lower rates of AKI and TIA.

“Even when we looked specifically at patients with type 2 diabetes, GLP-1a showed very [beneficial] results,” Cheema highlighted.

However, the study authors highlighted important limitations. Its observational, retrospective design precluded conclusions about causality, and the TriNetX database offered limited clinical granularity. Outcomes may have been under-ascertained when patients received care outside participating institutions, and there was the potential for misclassification or miscoding of diagnoses.

Despite these limitations, the findings suggested a potential therapeutic benefit of GLP-1a in patients with high-risk PV. Investigators noted that randomized controlled trials are warranted to confirm both the safety and efficacy of GLP-1a therapy in this population.

“Our study suggests a therapeutic benefit of GLP-1a in patients with PV…although randomized control trials are needed to confirm safety and efficacy in this high-risk population,” he concluded.

Reference

Cheema AY, Munir M, Mandala A, Aslam F, Acharya U. Glucagon-like peptide-1 agonists and clinical outcomes in polycythemia vera: a large-scale propensity-matched cohort study. Presented at 2025 Society of Hematologic Oncology Annual Meeting; September 3-6, 2025; Houston, TX. MPN-642.