Association between glucagon-like peptide-1 receptor agonist use and progression of monoclonal gammopathy of uncertain significance to multiple myeloma among patients with diabetes

Nikhil Grandhi, Lawrence Liu, Mei Wang, Theodore Thomas, Martin Schoen, Kristen Sanfilippo, Feng Gao, Graham A. Colditz, Kenneth R. Carson, Murali Janakiram, Su Hsin Chang*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Background: In patients with diabetes and monoclonal gammopathy of uncertain significance (MGUS), the impact of glucagon-like peptide-1 (GLP-1) receptor agonists on the natural history of MGUS is unknown. We aimed to assess the association of GLP-1 receptor agonist use in the progression of MGUS to multiple myeloma in patients with diabetes. Methods: This is a population-based cohort study of veterans diagnosed with MGUS from 2006 to 2021 with a prior diagnosis of diabetes. A validated natural language processing algorithm was used to confirm MGUS and progression to multiple myeloma. We performed 1:2 matching for individuals with and without GLP-1 receptor agonist exposure. The Gray test was performed to detect the difference in cumulative incidence functions for progression by GLP-1 receptor agonist use status. The association between time-varying GLP-1 receptor agonist use and progression was estimated through multivariable-adjusted hazard ratio using a stratified Fine-Gray distribution hazard model, with death as a competing event and stratum for the matched patient triad. Results: Our matched cohort included 1097 individuals with MGUS who had ever used GLP-1 receptor agonists and the matched 2194 patients who had never used GLP-1 receptor agonists. Overall, 2.6% of individuals progressed in the GLP-1 receptor agonist ever use group compared with 5.0% in the GLP-1 receptor agonist never use group. Cumulative incidence functions were statistically significantly different between the exposed and unexposed groups (P =. 02). GLP-1 receptor agonist use vs no use was associated with decreased progression to multiple myeloma (hazard ratio = 0.45, 95% confidence interval = 0.22 to 0.93, P =. 03). Conclusions: For patients with diabetes and MGUS, GLP-1 receptor agonist use is associated with a 55% reduction in risk of progression from MGUS to multiple myeloma compared with no use.

Original languageEnglish (US)
Article numberpkae095
JournalJNCI Cancer Spectrum
Volume8
Issue number6
DOIs
StatePublished - Dec 1 2024

Funding

This work was supported by the Foundation for Barnes-Jewish Hospital, the Siteman Cancer Center, and National Institutes of Health grants R01 CA253475 and U01 CA265735.

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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