GLP-1 Receptor Agonist Discontinuation Often Nonpermanent, Driven by Patient Behaviors and Healthcare System Factors

Type 2 diabetes mellitus and obesity are chronic conditions requiring long-term management, with GLP-1 receptor agonists (GLP-1RAs) emerging as highly effective treatments for glucose lowering and weight reduction. Despite their efficacy, many patients discontinue GLP-1RAs, leading to potential fluctuations in HbA1c and body weight, which are risk factors for cardiovascular and microvascular events. Understanding the reasons behind this discontinuation is crucial to optimize patient outcomes and ensure sustained therapeutic benefits, moving beyond simple medication-related adverse effects to encompass broader patient and systemic factors.

This narrative review systematically examined real-world, quantitative, and qualitative evidence regarding GLP-1RA discontinuation, adherence, and persistence. The authors aligned their findings with an established conceptual framework designed for understanding medication adherence in noncommunicable chronic diseases. The review aimed to synthesize existing literature, identify inconsistencies in definitions and study methodologies, and highlight understudied areas, particularly focusing on patient-related factors and the broader healthcare system context influencing long-term GLP-1RA use.

The review identified significant inconsistencies in how discontinuation, adherence, and persistence are defined and studied across the literature. Few qualitative studies have specifically focused on GLP-1RA discontinuation, limiting insights into patient experiences. Quantitative approaches often prioritize medication-related factors and superficial socioeconomic or condition-related aspects, with very few studies encompassing all 5 dimensions of the medication adherence conceptual framework. Patient-related factors, particularly patient behaviors, were found to be significantly understudied in relation to GLP-1RA discontinuation. Despite these challenges, a key finding was:

Patients treated for type 2 diabetes mellitus or weight management with GLP-1RAs often discontinue the medication, but this discontinuation is frequently nonpermanent. Improving adherence requires a nuanced understanding of care trajectories, GLP-1RA tolerability, patient expectations, and the integrated role of patient behaviors and the healthcare system.