Abstract 4358: Glucagon-like peptide 1 agonist use and the progression of monoclonal gammopathy of undetermined significance to multiple myeloma in US veterans with diabetes mellitus
Authors: Grandhi Nikhil , Liu Lawrence , Wang Mei , Thomas Theodore , Kumar Akhil , Vargo Kristin , Sanfilippo Kristen , Colditz Grahm , Chang Su-Hsin 
Published: April 2023

Abstract
Background: Glucagon-like peptide 1 (GLP-1) agonists are increasingly used in diabetics due to their cardiac and renal benefits along with their actions as antihyperglycemics. They also showed inhibitory effects in ovarian, breast, prostate, and pancreatic cancers in preclinical studies. However, to our knowledge, no studies have examined whether GLP-1 agonists have a similar effect in multiple myeloma. Using a population-based study design, we aimed to assess the association of GLP-1 agonist use in the progression of MGUS to MM in patients with diabetes mellitus (DM).
Methods: Patients diagnosed with MGUS from 1999-2021 in the Veterans Health Administration were identified via ICD codes and further confirmed by a natural language processing (NLP)-based algorithm. Progression to smoldering MM (sMM) or MM was also confirmed by another NLP-based algorithm. Only patients with DM, IgG, IgA, or light chain MGUS, and black and white patients were included. We excluded patients who experienced progression within 1 year of MGUS diagnosis or within 2 years of DM diagnosis, and patients diagnosed with MGUS before DM diagnosis. We performed 1:2 matching for patients with and without GLP-1 agonist exposure based on their follow-up time. Gray’s test was performed to detect the difference between the two cumulative incidence functions (CIF) for progression stratified by GLP-1 agonist use status. The association between GLP-1 agonist use and progression was estimated by multivariable-adjusted hazard ratio (aHR) using Fine-Gray distribution hazard model with death as a competing event and time-varying GLP-1 agonist use. The covariates included age, BMI, monoclonal protein (M-spike) level (≥1.5g/dL), creatinine (&gt;1.5 mg/dL), glycated hemoglobin (HbA1c; &lt; 7%, 7% - 9%, and &gt; 9%) at MGUS diagnosis, metformin and sodium-glucose co-transporter 2 inhibitor (SLGT2i) use, as well as sex, race, MGUS heavy chain subtype, light-chain MGUS, Charlson Comorbidity Index, and months from diagnoses of DM to MGUS.
Results: Our NLP algorithm confirmed 19,551 patients with DM and MGUS. After applying our inclusion and exclusion criteria, we had 14,832 patients, of which 1,303 had GLP-1 agonist use. After matching, our analytic cohort included 1,303 patients with exposure, and 2,606 patients without. There is no evidence to show that CIFs were different between the exposed and unexposed groups. However, the multivariable analysis showed that GLP-1 agonist use was associated with decreased progression to MM: aHR 0.35, 95% confidence interval 0.14-0.90, p = 0.03.
Conclusions: For DM patients with MGUS, GLP-1 agonist use is associated with a 65% reduction in risk of progression from MGUS to sMM/MM. Prospective studies examining whether GLP-1 agonists can be used as possible chemoprevention in MGUS patients with DM should be explored.
Citation Format: Nikhil Grandhi, Lawrence Liu, Mei Wang, Theodore Thomas, Akhil Kumar, Kristin Vargo, Kristen Sanfilippo, Grahm Colditz, Su-Hsin Chang. Glucagon-like peptide 1 agonist use and the progression of monoclonal gammopathy of undetermined significance to multiple myeloma in US veterans with diabetes mellitus. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 4358.