A real-world analysis on the impact of GLP-1 receptor agonist use on all-cause mortality and hematological outcomes in AML/CML patients with obesity

Abstract Introduction: Obesity is a known risk factor for poor outcomes in acute and chronic myeloid leukemia (AML/CML), and this adverse outcome is partly driven by obesity related inflammation, metabolic disruption, and altered drug response. With obesity rates rising amongst leukemia patients, effective management strategies are increasingly important. Studies have shown that glucagon-like peptide-1 receptor agonists (GLP-1 RAs), used for diabetes and weight loss, may offer additional benefits through anti-inflammatory and anti-neoplastic effects. This study is the first of its kind to explore the impact of GLP-1 RA use on all-cause mortality and hematological outcomes in obese AML/CML patients. Methodology: We conducted a retrospective cohort study using TriNetX, encompassing electronic health records from 142 healthcare organizations. Adult patients (18–90 years) with AML or CML (ICD-10: C92) and concurrent obesity (ICD-10: E66) were identified and divided into two cohorts: GLP-1 Users [prescribed GLP-1 RAs (ATC code A10BJ) (n=2,620)] and non-GLP-1 Users: [No GLP-1 exposure (n=24,240)]. Propensity score matching (1:1) adjusted for confounders and yielded 2,620 matched patients per cohort. The index event was the first date meeting the inclusion criteria. Outcomes were assessed from one day post-index onward. The primary endpoint was all-cause mortality, and the secondary endpoint was the incidence of hematological complications. Patients with outcomes before the study window were excluded. Multivariate analysis was utilized, and results were reported as odds ratios (OR), with 95% CI. Results The GLP-1 RA user cohort had a mean age of 61.4 ± 13.8 years and a mean index age of 58.3 ± 13.6 years. Of these patients, 54.7% were female and 42.5% male. Racial distribution was predominantly White (68.6%), followed by Black or African American (16.9%), Hispanic or Latino (8.2%), Asian (2.1%), and other races (3.6%). Demographics were similar in the control group. GLP-1 RA use was associated with significantly lower risk of all-cause mortality [15.0% vs. 26.0%; OR 0.50 (0.44–0.58)]. Additionally, GLP-1 RA use was associated with a reduced risk of anemia [21.6% vs. 28.8%; OR 0.68 (0.57–0.82)], thrombocytopenia [11.2% vs. 20.7%; OR 0.48 (0.40–0.58)], neutropenia [8.2% vs. 16.3%; OR 0.46 (0.38–0.56)], bone marrow failure [21.7% vs. 26.2%; OR 0.78 (0.63–0.97)], and venous thromboembolism [7.8% vs. 10.6%; OR 0.71 (0.58–0.88)]. No significant differences were observed for hemophagocytic lymphohistiocytosis or tumor lysis syndrome. Kaplan-Meier analyses confirmed improved survival in the GLP-1RA cohort for all-cause mortality and key hematologic outcomes. Conclusion: In this real-world analysis, GLP-1 receptor agonist use was associated with significantly reduced all-cause mortality and improved hematologic outcomes in obese patients with AML/CML. These findings suggest that GLP-1 RAs may offer meaningful clinical benefits beyond metabolic control, potentially serving as adjunctive therapy in this high-risk population. Further prospective studies are warranted to confirm these associations and explore underlying mechanisms.