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

Hitoshi Ishii, Brian B Hansen, Jakob Langer, Hiroshi Horio, Hitoshi Ishii, Brian B Hansen, Jakob Langer, Hiroshi Horio

Abstract

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.

Keywords: Clinical trial; Diabetes Treatment-Related Quality of Life; Dulaglutide; GLP-1 receptor agonist; Health-related quality of life; Japan; Orally administered semaglutide; Phase 3; Type 2 diabetes.

Figures

Fig. 1
Fig. 1
Estimated changes from baseline in DTR-QoL domain scores at weeks 26 and 52 for the treatment policy estimand. (i) Burden on social activities and daily activities; (ii) anxiety and dissatisfaction with treatment; (iii) hypoglycemia; (iv) satisfaction with treatment; and (v) total score. Data are for the treatment policy estimand. Missing post-baseline values were imputed by a pattern mixture model using multiple imputation. Pattern was defined by treatment arm and treatment status (premature trial product discontinuation and/or initiation of rescue medication), and imputations were based on an ANCOVA model. Imputation was from own treatment arm and same treatment status. Change from baseline was analyzed using an ANCOVA model with treatment and strata as categorical fixed effects and baseline value as the covariate for each of the 1000 imputed complete datasets, and pooled by Rubin’s rule to draw inference [30]. No statistical analyses were controlled for multiplicity as there are no confirmatory endpoints. aLower bound of 95% confidence interval > 0 for the estimated treatment difference vs dulaglutide 0.75 mg, favoring orally administered semaglutide. ANCOVA analysis of covariance, DTR-QoL Diabetes Therapy-Related Quality of Life

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