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

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. Supplementary Information The online version contains supplementary material available at 10.1007/s13300-020-00985-w.

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“…The safety profile of 2.4 mg semaglutide was similar to that of 1.0 mg SC semaglutide and oral semaglutide, with predominant gastrointestinal (GI) disease symptoms that were mild to moderate, with not many reports of hypoglycemia. The PIONEER (Peptide Innovation for Early Diabetes Treatment) clinical trial program 35 – 44 not only showcased a significant decrease in both glycosylated hemoglobin (HbA1c) and body weight with oral semaglutide when compared with placebo but also proved superior to other oral antidiabetic medications like sitagliptin and empagliflozin along with agents from its own drug class like dulaglutide and liraglutide.…”

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“…This suggests that the premature discontinuation of oral semaglutide in trials may also be due to patients’ expectations at the start of treatment and lack of counseling that effects such as nausea are frequent experiences that typically disappear over time. However, a recent Japanese health-related quality of life assessment of the PIONEER-10 trial showed that patients tended to be more satisfied when treated with oral semaglutide than with injectable dulaglutide ( Ishii et al, 2021 ). Patients treated with oral semaglutide were also more adherent to the treatment ( Ishii et al, 2021 ).…”

“…However, a recent Japanese health-related quality of life assessment of the PIONEER-10 trial showed that patients tended to be more satisfied when treated with oral semaglutide than with injectable dulaglutide ( Ishii et al, 2021 ). Patients treated with oral semaglutide were also more adherent to the treatment ( Ishii et al, 2021 ). This suggests that oral GLP-1 receptor agonists, compared to injectable GLP-1 receptor agonists, result in greater patient satisfaction and treatment persistence.…”

“…; per oral, s.c.; subcutaneous. *Based on a Japanese diabetes treatment related quality of life questionnaire oral semaglutide seemed to be preferred over injectable dulaglutide (i.e., injectable GLP-1R agonist) by the participating patients ( Ishii et al, 2021 ). …”

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“…The efficacy of oral semaglutide has been demonstrated in the phase 3 PIONEER (Peptide InnOvatioN for Early diabEtes tReatment) clinical programme, involving patients with T2DM treated with oral semaglutide monotherapy through insulin add-on for up to 78 weeks in global populations and two trials on Japanese populations only [10]. Oral semaglutide was more efficacious with a greater reduction in HbA 1c and greater or similar weight reductions compared with a dipeptidyl peptidase-4 inhibitor (sitagliptin), a sodium-glucose cotransporter-2 inhibitor (empagliflozin), or placebo, and in a Japanese study compared with the once-weekly subcutaneous GLP-1RA dulaglutide [11][12][13][14][15][16][17]. The efficacy of oral semaglutide is non-inferior to the injectable GLP-1RA liraglutide [12,16].…”