Rates of, Reasons for, and Reactions to Discontinuation of GLP-1 Receptor Agonists: A Narrative Review

GLP-1RAs are increasingly used for their glucose-lowering and weight-management effects, but many patients discontinue them. In this narrative review we aim to review real-world, quantitative and qualitative GLP-1RA discontinuation, adherence, and persistence evidence as it aligns with an established conceptual framework for understanding medication adherence in noncommunicable chronic disease. Many inconsistencies exist in how discontinuation, adherence, and persistence are studied in this literature. Few qualitative studies have focused on discontinuation of GLP-1RAs. Quantitative approaches often focus on medication-related factors and more superficial aspects of socioeconomic and condition-related factors. Very few studies encompass all 5 dimensions of the medication adherence conceptual framework. Patient-related factors, especially related to patient behaviors, are understudied in relation to GLP-1RA discontinuation. Patients treated for type 2 diabetes mellitus or weight management with GLP-1RAs often discontinue the medication, but this is often nonpermanent. Improving adherence to and persistence on GLP-1RAs will require nuanced attention to care trajectories as well as an integrated understanding of GLP-1RA tolerability, expectations, and the understudied role of patient behaviors and the healthcare system. To clarify relevant mechanisms and guide targeted intervention for highest-risk individuals, further study should standardize definitions of persistence and discontinuation and implement patient-centered qualitative work, especially related to health behaviors.