Adherence Patterns of Oral vs Injectable GLP-1 Receptor Agonists: A National Real-World Analysis of Commercial Claims Data, 2010–2021

Background: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are increasingly important in managing type 2 diabetes and obesity, but their effectiveness is limited by adherence challenges. While once-weekly injectable formulations may improve adherence compared to daily options, comparative data between oral and injectable GLP-1RAs remains limited. Objective: To compare real-world adherence patterns between oral and injectable GLP-1RAs using a large national claims database. Methods: This retrospective study analyzed 78,297 commercially insured adults (median age 53 years, 55.3% female) who initiated GLP-1RA therapy between 2010-2021, using the IQVIA PharMetrics® Plus database. Medication adherence was assessed via proportion of days covered (PDC), with PDC ≥80% indicating high adherence, at both 6-month and 12-month intervals. Treatment discontinuation was defined as a gap exceeding 90 consecutive days in prescription fills. Results: Most prescriptions were for injectable formulations (98.9%), with only 1.1% for oral semaglutide. At six months, mean PDC values ranged from 58.0% for exenatide injection to 69.5% for dulaglutide. The proportion of patients achieving high adherence varied from 28.0% for liraglutide/insulin degludec to 49.7% for dulaglutide. At one year, oral semaglutide demonstrated the highest mean PDC (82.4%) and proportion of patients with high adherence (65.1%), followed by dulaglutide (59.1%). Conclusions: In this large, real-world cohort, six-month adherence to oral semaglutide exceeded that of most injectable GLP-1RAs except dulaglutide. At one year, oral semaglutide demonstrated superior adherence compared to all injectable formulations, suggesting that after the initial period of potential gastrointestinal side effects, the convenience of oral administration may enhance long-term persistence. Limitations: Study limitations include lack of clinical parameters, a small oral semaglutide sample (1.1%), and restriction to commercially insured individuals aged 18-65 years.