Objective This study aimed to evaluate the impact of socioeconomic disparities on the allocation of second-line treatments among patients with type 2 diabetes (T2D).

Materials and Methods We conducted an observational study using real-world data from over 9 million patients across five University of California Health centers. The study included patients who initiated a second-line T2D medication after metformin, with hemoglobin A1c (HbA1c) measurements within ±7 days of treatment initiation from 2012 through September 2024. Multinomial regression models assessed the association between socioeconomic status and second-line treatment choices. Additionally, we used the GPT-4 large language model with a zero-shot learning approach to analyze 270 clinical notes from 105 UCSF patients. GPT-4 identified adverse social determinants of health (SDOH) across six domains: transportation, housing, relationships, patients with children, support, and employment.

Results Among 15,090 patients (56.7% male, 43.3% female; mean age 59.3 years; mean HbA1c 8.91%), second-line treatments included sulfonylureas (SUs; n = 6,732), DPP4 inhibitors (n = 2,918), GLP-1 receptor agonists (n = 2,736), and SGLT2 inhibitors (n = 2,704). Patients from lower socioeconomic neighborhoods were more likely to receive SUs over other medications: DPP4i (OR = 0.96, [95% CI, 0.95-0.98]), GLP-1RA (OR = 0.94, [95% CI, 0.92-0.96]), SGLT2i (OR = 0.95, [95% CI, 0.93-0.97]). In UCSF clinical notes, we identified adverse SDOH including housing (n=8), transportation (n=1), relationships (n=22), employment (n=12), support (n=1), and patients with children (n=25).

Conclusions Socioeconomic factors influence second-line T2D treatment choices. Addressing these disparities is essential to ensuring equitable access to advanced T2D therapies.

Kendra Radtke is a current employee and shareholder of Genentech/Roche. Atul Butte is a co-founder and consultant to Personalis and NuMedii; consultant to Mango Tree Corporation, and in the recent past, Samsung, 10x Genomics, Helix, Pathway Genomics, and Verinata (Illumina); has served on paid advisory panels or boards for Geisinger Health, Regenstrief Institute, Gerson Lehman Group, AlphaSights, Covance, Novartis, Genentech, Merck, and Roche; is a shareholder in Personalis and NuMedii; is a minor shareholder in Apple, Meta (Facebook), Alphabet (Google), Microsoft, Amazon, Snap, 10x Genomics, Illumina, Regeneron, Sanofi, Pfizer, Royalty Pharma, Moderna, Sutro, Doximity, BioNtech, Invitae, Pacific Biosciences, Editas Medicine, Nuna Health, Assay Depot, and Vet24seven, and several other non-health-related companies and mutual funds; and has received honoraria and travel reimbursement for invited talks from Johnson and Johnson, Roche, Genentech, Pfizer, Merck, Lilly, Takeda, Varian, Mars, Siemens, Optum, Abbott, Celgene, AstraZeneca, AbbVie, Westat, and many academic institutions, medical or disease-specific foundations and associations, and health systems. Atul Butte receives royalty payments through Stanford University for several patents and other disclosures licensed to NuMedii and Personalis. Atul Buttes research has been funded by NIH, Peraton (as the prime on an NIH contract), Genentech, Johnson and Johnson, FDA, Robert Wood Johnson Foundation, Leon Lowenstein Foundation, Intervalien Foundation, Priscilla Chan and Mark Zuckerberg, the Barbara and Gerson Bakar Foundation, and in the recent past, the March of Dimes, Juvenile Diabetes Research Foundation, California Governors Office of Planning and Research, California Institute for Regenerative Medicine, LOreal, and Progenity.

Research reported in this publication was supported by the UCSF Bakar Computational Health Sciences Institute, and the National Center for Advancing Translational Sciences, National Institutes of Health, through UCSF CTSI grant number UL1 TR001872, along with the Food and Drug Administration, through U01 FD005978 to the UCSF Stanford Center of Excellence in Regulatory Sciences and Innovation (CERSI). Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the NIH or FDA. None of the study sponsors had any influence over the data interpretation or conclusions of this study.

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