Abstract 1960: Racial differences in the association of metformin use with progression of monoclonal gammopathy of undetermined significance to multiple myeloma in US veterans with diabetes mellitus
Authors: Liu Lawrence W. , Grandhi Nikhil , Wang Mei , Thomas Theodore , Kumar Akhil , Vargo Kristin , Sanfilippo Kristen M. , Colditz Graham , Chang Su-Hsin 
Published: April 2023

Abstract
Background: Metformin is an oral antihyperglycemic with possible antineoplastic properties based on preclinical and retrospective studies. A retrospective study of Veterans demonstrated a reduction in monoclonal gammopathy of undetermined significance (MGUS) to multiple myeloma (MM) progression in patients with diabetes mellitus (DM) treated with metformin for ≥4 years. However, it is unclear whether there are racial differences to this effect of metformin.
Methods: Patients diagnosed with MGUS from 1999-2021 in the Veterans Health Administration were identified. We used a natural language processing-based algorithm to confirm MGUS diagnosis and progression, including smoldering MM and MM. Only patients with DM, IgG, IgA, or light chain MGUS, and black and white patients were included in the analyses. We excluded patients who experienced progression within 6 months of MGUS diagnosis, patients who were diagnosed with MGUS before DM diagnosis, and patients who died, progressed to MM, or were lost to follow up within four years of MGUS diagnosis. We defined metformin users as those who had metformin use for ≥4 years after DM diagnosis and before MM development. Cumulative incidence functions (CIF) were stratified by metformin use status. Gray’s test was performed to detect the difference between the two functions. The association between metformin use and progression was estimated by multivariable-adjusted hazard ratio (aHR) using Fine-Gray distribution hazard model with death as a competing event. The covariates included age, BMI, monoclonal protein (M-spike) level (≥1.5g/dL), creatinine, and glycated hemoglobin (HbA1c) at MGUS diagnosis, as well as sex, race, MGUS heavy chain subtype, light-chain MGUS, and Charlson Comorbidity Index.
Results: Our NLP algorithm confirmed 19,551 patients with DM and MGUS. After applying our inclusion and exclusion criteria, we had 13,068 (35% black and 65% white) patients of which, 4,268 (26.2% black and 36.2% white) were metformin users. Cumulative incidence function was stratified by metformin use status were statistically significant different (p=0.04) with a lower progression rate for metformin users (see Fig). The multivariable analysis demonstrated a statistically significant reduction in progression with metformin use in the overall cohort (aHR 0.79; 95% CI 0.67-0.95). Further multivariable analyses showed that metformin use was associated with a significant reduction in progression rate in white patients (aHR 0.73; 95% CI 0.58-0.91) but not in black patients (aHR 0.90; 95% CI 0.69-1.17).
Conclusions: For patients with DM and MGUS, ≥4 years of metformin use was associated with a reduced risk of progression of MGUS to MM in white patients but not in black patients.
Citation Format: Lawrence W. Liu, Nikhil Grandhi, Mei Wang, Theodore Thomas, Akhil Kumar, Kristin Vargo, Kristen M. Sanfilippo, Graham Colditz, Su-Hsin Chang. Racial differences in the association of metformin use with 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 1960.