Adherence, Persistence and Discontinuation of Incretin Mimetics and Sodium Glucose Transporter 2 Inhibitors: A Narrative Review

Type 2 diabetes mellitus (T2D) requires long-term pharmacological management, and real-world treatment effectiveness depends critically on adherence, persistence and the appropriate management of discontinuation. This narrative review examines the evidence on these three dimensions of medication-taking behaviour, with a focus on glucagon-like peptide-1 receptor agonists (GLP-1RAs), the dual glucose-dependent insulinotropic polypeptide (GIP)/GLP-1 receptor agonist tirzepatide and sodium-glucose cotransporter-2 inhibitors (SGLT2i), whose cardiorenal and metabolic benefits can only be realized if treatment is initiated and maintained over time. We discuss the heterogeneity of adherence and persistence definitions and measurement methods. Roughly half of patients with T2D achieve commonly used adherence thresholds, and both adherence and persistence decline over time; suboptimal adherence is associated with poorer glycaemic control and higher rates of hospitalization and mortality. Once-weekly GLP-1RA formulations are generally associated with better persistence than daily or oral regimens, whereas SGLT2i adherence is comparable to, or in some cohorts better than, that of GLP-1RAs. Current data do not show that dual agonism improves tolerability or persistence. Discontinuation is frequent, often temporary, sometimes clinically appropriate and, when unplanned, associated with loss of metabolic and cardiorenal benefit. We review strategies to improve adherence and persistence, including education, proactive management of adverse effects, early follow-up, attention to emotional well-being and multicomponent interventions, and argue for a person-centred approach that identifies individual barriers rather than labelling patients as “non-adherent”.