Incorporating Treatment Pauses, Dosing Flexibility and Education to Support GLP-1RA Therapy Persistence

Abstract

As the first oral GLP-1 receptor agonist (GLP-1RA), oral semaglutide may increase accessibility of GLP-1RA therapy in broader care settings. Understanding the management of GLP-1RA therapy when intolerability occurs, including gastrointestinal (GI) adverse events (AEs), is important to maintain treatment persistence. The PIONEER 6 trial (NCT02692716; N=3183) examined the efficacy and safety of oral semaglutide in patients with type 2 diabetes either ≥50 years with established cardiovascular/kidney disease or ≥60 years with cardiovascular risk factors. While 27% of patients temporarily discontinued semaglutide on ≥1 occasion during the trial, 12% permanently discontinued due to AE(s). We evaluated medication management strategies within PIONEER 6 to assess their role in supporting treatment continuation. Patients taking semaglutide underwent dose escalation (initiation, 3 mg; 4 weeks, 7 mg; 8 weeks, 14 mg). Investigators could reduce the dose if AEs developed and re-escalate once symptoms resolved/diminished. Patients were educated to address GI AEs throughout the trial. Patients who discontinued treatment because of AEs were encouraged to resume treatment once the AE had ceased. If patients discontinued semaglutide for >21 days, re-escalation from a lower dose was recommended to mitigate GI AEs. Discontinuation mostly occurred during the initial dose escalation period. In total, 23% of patients receiving semaglutide had ≥1 treatment pause, of which, 72% had one pause. Median duration of treatment pause was 21 days. Importantly, 75% of patients restarted semaglutide after the first AE-related treatment discontinuation. These data highlight the role of treatment pauses, flexibility and education in mitigating potential AEs to support treatment persistence on GLP-1RAs.