Anastasios Tentolouris, Ioannis Ntanasis‐Stathopoulos, Charalampos Filippatos, Evangelos Terpos, Efstathios Kastritis, Ernesto Ruiz Duque, Meletios Α. Dimopoulos, Maria Gavriatopoulou, Αlexandros Briasoulis
BACKGROUND: Monoclonal gammopathy of undetermined significance (MGUS) is a premalignant plasma cell disorder with potential progression to multiple myeloma (MM). Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have demonstrated potential anti-neoplastic properties. This study evaluated the association between GLP-1 RA use and clinical outcomes in individuals with MGUS and concurrent DM, overweight or obesity. METHODS: A retrospective cohort study was conducted using the TriNetX global health research network. Adults with MGUS and either DM or overweight/obesity were identified. Propensity score matching (1:1) was performed, resulting in two balanced cohorts. The primary outcome was progression-free survival (PFS). Secondary outcomes included overall survival (OS), time to progression to multiple myeloma (MM) and major cardiovascular events, including myocardial infarction (MI), ischemic stroke, ischemic heart disease and heart failure (HF). RESULTS: Among 30,034 matched patients, 823 patients in the GLP-1 RA group and 2317 in the control group progressed to symptomatic MM or died. GLP-1 RA use was associated with significantly improved PFS [HR (95% CI): .63 (.58-.68)] and OS [HR (95% CI): .61 (.56-.66)]. A reduced risk of progression to symptomatic MM was also observed [HR (95% CI): .82 (.69-.98)]. GLP-1 RA users had lower cumulative incidence of MI, HF, ischemic heart disease, and stroke; however, these differences were not confirmed in time-to-event analyses. CONCLUSIONS: GLP-1 RA therapy was associated with significantly improved PFS and OS in MGUS patients with metabolic comorbidities. While fewer cardiovascular events were observed, these findings were not statistically confirmed over time.