Diabetes, Metabolic Syndrome and Obesity · Oct 12, 2026

Adherence and Persistence to Injectable versus Oral GLP-1 Receptor Agonists in Patients with Type 2 Diabetes Mellitus: A Comparative Systematic Review and Analysis

By Ashour AM

BACKGROUND: Type 2 diabetes mellitus (T2DM) requires sustained glycemic control to prevent long-term complications. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are effective therapies, traditionally administered via injection. The introduction of oral formulations, such as oral semaglutide, may improve patient adherence and persistence. METHODS: A systematic review with descriptive pooled synthesis was conducted using studies identified from PubMed, ClinicalTrials.gov, and relevant real-world observational data sources. Adherence and persistence outcomes were summarized and compared descriptively between injectable and oral GLP-1 RAs. RESULTS: Across the included total of 13 studies and medical records, data from 1348 patients were summarized. Oral GLP-1 RAs were associated with higher reported adherence (70.8% vs 62.4%) and persistence (62.1% vs 47.8%) compared with injectable formulations. A chi-square test of independence showed that the difference in adherence between oral and injectable GLP-1 was significant; (χ ² = 10.8, p < 0.01). Similarly, chi-square test showed that the observed variation in persistence between Oral-GLP vs injectable GLP-1 was also significant (χ ² = 37.9, p < 0.001). Injectable therapies were associated with higher rates of adverse events, particularly injection-site reactions. CONCLUSION: Oral GLP-1 RAs may be associated with improved adherence and persistence in patients with T2DM. These findings suggest that formulation choice may influence long-term diabetes treatment continuation, although further study-level meta-analytic research is needed.

doi.org/10.2147/dmso.s614243 Open access PubMed 42893177 Interventions