Effect of Orally Administered Semaglutide Versus Dulaglutide on Diabetes-Related Quality of Life in Japanese Patients with Type 2 Diabetes: The PIONEER 10 Randomized, Active-Controlled Trial.

Introduction In the randomized Peptide InnOvatioN for Early diabEtes tReatment (PIONEER) 10 trial, once-daily orally administered semaglutide-the first oral glucagon-like peptide 1 receptor agonist (GLP-1RA)-was similarly tolerated with comparable (at 7 mg) or better (at 14 mg) efficacy versus the injectable GLP-1RA dulaglutide 0.75 mg. Health-related quality of life (HRQoL) in PIONEER 10 was assessed using the Japanese-specific Diabetes Therapy-Related Quality of Life (DTR-QoL) questionnaire. Methods The DTR-QoL comprises 29 questions, providing four domain and total scores. Answers were converted to a score between 0 and 100, with higher scores indicating greater HRQoL. Two estimands were prespecified: treatment policy (regardless of treatment discontinuation or rescue medication use) and trial product (assuming on treatment without rescue medication) in all randomized patients. Outcomes were assessed at weeks 26 and 52. Results Mean baseline DTR-QoL domain scores were similar between treatment arms and were generally lower (giving more scope for improvement) for "anxiety and dissatisfaction with treatment" (62.1-65.3) and "satisfaction with treatment" (53.9-57.9) than "burden on social activities and daily activities" (76.5-77.7) and "hypoglycemia" (83.5-88.2). Using the treatment policy estimand, orally administered semaglutide 7 and 14 mg improved HRQoL versus dulaglutide 0.75 mg for the total score (estimated mean change from baseline [CfB] 7.3 and 8.1 vs 3.3; estimated treatment difference [ETD] 3.9 and 4.8) and the "anxiety and dissatisfaction with treatment" domain (CfB 9.7 and 10.9 vs 3.7; ETD 6.0 and 7.2) at week 52. Orally administered semaglutide 14 mg improved the "satisfaction with treatment" domain versus dulaglutide 0.75 mg (CFB 13.8 vs 5.7; ETD 8.1). DTR-QoL scores for orally administered semaglutide tended to be more durable (sustained over time) than for dulaglutide. Outcomes for the trial product estimand were similar. Conclusion Orally administered semaglutide 7 and 14 mg improved the patients' HRQoL measured by the Japanese-specific DTR-QoL instrument versus dulaglutide 0.75 mg at week 52. Trial registration ClinicalTrials.gov NCT03015220.