Conference Coverage

GLP-1 Receptor Agonist Use Linked to Lower Risk of MGUS Progression in Large US Cohort

Edited by:
Ashton L. Stahl

Key Highlights

  • GLP-1 receptor agonist use was associated with reduced progression from monoclonal gammopathy of undetermined significance to smoldering multiple myeloma (SMM) and from SMM to multiple myeloma.
  • Propensity-matched analyses included > 6,000 MGUS patients and > 2,000 SMM patients.
  • Hazard ratios favored GLP-1 receptor agonist exposure across both primary and secondary outcomes.

New findings presented at the 67th ASH Annual Meeting and Exposition suggest that exposure to GLP-1 receptor agonists may be associated with a substantially lower risk of disease progression among patients with premalignant plasma cell disorders. The research examined whether these widely used agents in metabolic disease management may influence progression pathways in monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma (SMM), conditions with limited modifiable risk factors.

Investigators used the TriNetX Research Network, a large multi-institutional database of de-identified electronic health records, to identify adults diagnosed with MGUS between January 2006 and July 2025. Two propensity-matched cohorts were created for the primary analysis: MGUS patients exposed to GLP-1 receptor agonists and those without exposure. Patients with prior SMM or multiple myeloma (MM) were excluded. The primary endpoint was progression from MGUS to SMM.

A secondary analysis evaluated a distinct matched cohort of patients with SMM to assess progression to MM. Propensity score matching (1:1) incorporated demographics, comorbid conditions, including diabetes, hypertension, chronic kidney disease, obesity, and hyperlipidemia, and laboratory markers, such as M-protein, erythrocyte sedimentation rate, C-reactive protein, albumin, beta-2 microglobulin, and total protein. Researchers calculated risk measures and generated Kaplan-Meier curves and Cox proportional hazards models.

Study Findings

In the primary analysis, 6,560 GLP-1 receptor agonist users were matched with 6,894 non-users. Progression from MGUS to SMM occurred in 2.80% of GLP-1 users versus 10.42% of non-users, yielding a risk difference of –7.61% and a hazard ratio (HR) of 0.30 (95% CI, 0.26–0.36; P < 0.0001).

The secondary SMM cohort included 2,218 GLP-1 receptor agonist users and 3,036 non-users. Progression from SMM to MM occurred in 11.50% of GLP-1 users versus 20.37% of non-users, corresponding to a risk difference of –8.86% and an HR of 0.63 (95% CI, 0.54–0.73; P < 0.0001). Kaplan-Meier curves demonstrated significantly improved progression-free survival for GLP-1 receptor agonist users in both analyses. A multivariable Cox model applied to the whole cohort further supported a reduced risk of progression (HR 0.65; 95% CI, 0.58–0.74).

Clinical Implications

According to the study authors, the findings suggest that use of GLP-1 receptor agonists may be associated with a lower likelihood of progression from MGUS to SMM or MM. They noted that these real-world results highlight the need for prospective trials evaluating GLP-1 receptor agonists as a potential chemopreventive strategy in plasma cell dyscrasias.

Expert Commentary

“The observed association may also show the impact of GLP-1 receptor agonists on obesity-related and inflammatory pathways, supporting ongoing research into the metabolic and immunologic drivers of multiple myeloma progression,” the researchers concluded.

Reference

Abidi A, Mann H, Purvey S, et al. GLP-1 receptor agonist use is associated with lower risk of progression from MGUS to SMM or MM in a large real-world cohort. 67th ASH Annual Meeting and Exposition; Orlando, FL. December 6-9. Accessed December 5, 2025. https://submit.hematology.org/program/presentation/671446.