Impact of Adjuvant GLP-1RA Treatment on the Adherence of Second-Generation Antipsychotics in Nondiabetic Adults

Background: Second-generation antipsychotics (SGA) are well known to frequently cause weight gain, increasing cardiometabolic risk, and reducing medication adherence. Glucagon-like peptide-1 receptor agonists (GLP-1RA) mitigate weight gain in controlled settings, but their real-world impact on SGA adherence remains unexplored. This study evaluated the role of adjuvant GLP-1RA treatment in improving SGA adherence among nondiabetic adults. Methods: A retrospective cohort study using the MarketScan Commercial and Medicaid claims database (2019-2023) identified nondiabetic adult patients initiating GLP-1RA following an SGA prescription, with ≥60 days overlap between SGA and GLP-1RA prescription fills (Adjuvant GLP-1RA users). Eligible patients were continuously enrolled 90 days pre-GLP-1RA and 180 days post-GLP-1RA initiation (index date). Prescription-time-distribution matching addressed immortal time bias and assigned an index date to SGA-only users. Propensity score matching (PSM) adjusted for baseline covariates. Results: This study identified 2153 eligible patients in the commercial and 787 in the Medicaid subgroups. Compared with SGA-only users, adjuvant GLP-1-RA users achieved a higher mean proportion of days covered (PDC; 74.30% vs 66.91%) and longer persistence (165.6 vs 139.2 d). Medicaid patients showed similar benefits (PDC: 88.25% vs 70.32%; persistence: 162.1 vs 122.1 d). PSM adjusted models demonstrated that the difference in PDC between the study groups was 8.91% (commercial) and 19.80% (Medicaid), with corresponding differences in persistence of 27.12 and 41.21 days. The effect was consistent both when the follow-up period was extended to 365 days and when examined across individual GLP-1RA agents. Conclusions: Adjuvant GLP-1RA is associated with improved PDC and adherence to SGA in nondiabetic adults.