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

Abstract

Background In patients with diabetes mellitus (DM) and monoclonal gammopathy of undetermined significance (MGUS), the impact of GLP-1 receptor agonists (GLP-1RAs) on the natural history of MGUS is unknown. We aimed to assess the association of GLP-1RA use in the progression of MGUS to multiple myeloma (MM) in patients with DM. Methods This is a population-based cohort study of Veterans diagnosed with MGUS from 2006-2021 with a prior diagnosis of DM. A validated natural language processing-algorithm was used to confirm MGUS and progression to MM. Gray’s test was performed to detect the difference in cumulative Incidence functions (CIFs) for progression by GLP-1RA use status. The association between time-varying GLP-1RA use and progression was estimated in the 1 (exposed):2 (unexposed) matched cohort via multivariable-adjusted hazard ratio (aHR) using stratified Fine-Gray distribution hazard model with death as a competing event and stratum for the matched patient triad. Results Our analytic cohort included 1,097 MGUS patients who ever used GLP-1RAs, and the matched 2,194 patients who never used GLP-1RAs. Overall, 2.55% progressed in the GLP-1RA ever use group, compared to 5.01% in the GLP-1RA never use group. CIFs were significantly different between the exposed and unexposed groups (P = .02). GLP-1RA use, compared to no-use, was associated with decreased progression to MM (aHR 0.45, 95% confidence interval 0.22 to 0.93, P = .03). Conclusions For patients with DM and MGUS, GLP-1RA use is associated with a 55% reduction in risk of progression from MGUS to MM, compared to no use.