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GLP-1 receptor agonists in patients with MGUS: A real-world propensity-matched study

Anastasios Tentolouris1, Ioannis Ntanasis-Stathopoulos2, Charalampos Filippatos2

  • 1First Department of Propaedeutic Internal Medicine and Diabetes Center, School of Medicine, National and Kapodistrian University of Athens, Laiko General Hospital, Athens, Greece.

European Journal of Clinical Investigation
|October 22, 2025
PubMed
Abstract

Insights

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) improved progression-free survival and overall survival in patients with monoclonal gammopathy of undetermined significance (MGUS) and metabolic conditions. GLP-1 RA use also showed a reduced risk of progression to multiple myeloma.

Area of Science:

  • Oncology
  • Pharmacology
  • Metabolic Diseases

Background:

  • Monoclonal gammopathy of undetermined significance (MGUS) is a premalignant plasma cell disorder that can progress to multiple myeloma (MM).
  • Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) exhibit potential anti-neoplastic effects.
  • This study investigates GLP-1 RA use in MGUS patients with diabetes mellitus (DM), overweight, or obesity.

Purpose of the Study:

  • To evaluate the association between GLP-1 RA use and clinical outcomes in MGUS patients with concurrent metabolic conditions.
  • To assess the impact of GLP-1 RAs on progression-free survival (PFS) and overall survival (OS).
  • To examine the effect on time to progression to multiple myeloma (MM) and major adverse cardiovascular events (MACE).

Main Methods:

  • Retrospective cohort study utilizing the TriNetX global health research network.
  • Identification of adult MGUS patients with DM, overweight, or obesity.
  • Propensity score matching (1:1) to create balanced cohorts for analysis.

Main Results:

  • GLP-1 RA use was linked to significantly improved PFS (HR: 0.63) and OS (HR: 0.61).
  • A reduced risk of progression to symptomatic MM was observed in GLP-1 RA users (HR: 0.82).
  • While fewer cardiovascular events were noted, these did not reach statistical significance in time-to-event analyses.

Conclusions:

  • GLP-1 RA therapy demonstrates significant benefits in PFS and OS for MGUS patients with metabolic comorbidities.
  • The potential cardiovascular benefits require further investigation.
  • GLP-1 RAs may offer a therapeutic option for managing MGUS in patients with metabolic conditions.
Keywords:
GLP‐1 receptor agonistscardiovascular outcomesdiabetes mellitusmonoclonal gammopathy of undetermined significancemultiple myelomaobesity

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