Association between GLP-1RA use and progression of MGUS to Multiple Myeloma among diabetic patients.

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.