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Efficacy and safety of oral semaglutide monotherapy vs placebo in a predominantly Chinese population with type 2 diabetes (PIONEER 11): a double-blind, Phase IIIa, randomised trial

Weiqing Wang Orcid Logo, Steve Bain Orcid Logo, Fang Bian Orcid Logo, Rui Chen Orcid Logo, Sanaz Gabery Orcid Logo, Shan Huang Orcid Logo, Thomas B. Jensen Orcid Logo, Bifen Luo Orcid Logo, Guoyue Yuan Orcid Logo, Guang Ning Orcid Logo

Diabetologia, Volume: 67, Pages: 1783 - 1799

Swansea University Author: Steve Bain Orcid Logo

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DOI (Published version): 10.1007/s00125-024-06142-3

Abstract

Aims/hypothesis: The aim of this study was to evaluate the efficacy and safety of oral semaglutide monotherapy vs placebo in a predominantly Chinese population with type 2 diabetes insufficiently controlled with diet and exercise alone. Methods: The Peptide Innovation for Early Diabetes Treatment (P...

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Published in: Diabetologia
ISSN: 0012-186X 1432-0428
Published: Springer Nature 2024
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Methods: The Peptide Innovation for Early Diabetes Treatment (PIONEER) 11 trial was a double-blind, randomised, Phase IIIa trial conducted across 52 sites in the China region (mainland China and Taiwan), Hungary, Serbia and Ukraine. Eligible participants were ≥18 years (≥20 years in Taiwan), had a diagnosis of type 2 diabetes with HbA1c 53–86 mmol/mol (7.0–10.0%) and were not receiving any glucose-lowering drugs. After a 4-week run-in period in which participants were treated with diet and exercise alone, those who fulfilled the randomisation criteria were randomised (1:1:1:1) using a web-based randomisation system to receive once-daily oral semaglutide 3 mg, 7 mg or 14 mg or placebo for 26 weeks (using a 4-week dose-escalation regimen for the higher doses). Randomisation was stratified according to whether participants were from the China region or elsewhere. The primary and confirmatory secondary endpoints were change from baseline to week 26 in HbA1c and body weight (kg), respectively. Safety was assessed in all participants exposed to at least one dose of the trial product. Results: Between October 2019 and October 2021, a total of 774 participants were screened and 521 participants were randomised to oral semaglutide 3 mg (n=130), 7 mg (n=130), 14 mg (n=130) or placebo (n=131); most participants (92.5%, n=482) completed the trial, with 39 participants prematurely discontinuing treatment. The number of participants contributing to the trial analyses was based on the total number of participants who were randomised at the beginning of the trial. The majority of participants were male (63.7%), and the mean age of participants was 52 years. At baseline, mean HbA1c and body weight were 63 mmol/mol (8.0%) and 79.6 kg, respectively. Oral semaglutide resulted in significantly greater reductions in HbA1c than placebo at week 26 (p&lt;0.001 for all doses). The estimated treatment differences (ETDs [95% CIs]) for oral semaglutide 3 mg, 7 mg and 14 mg vs placebo were –11 (–13, –9) mmol/mol, –16 (–18, –13) mmol/mol and –17 (–19, –15) mmol/mol, respectively. The corresponding ETDs in percentage points (95% CI) vs placebo were –1.0 (–1.2, –0.8), –1.4 (–1.6, –1.2) and –1.5 (–1.8, –1.3), respectively. Significantly greater reductions in body weight were also observed for oral semaglutide 7 mg and 14 mg than for placebo at week 26 (ETD [95% CI] –1.2 kg [–2.0 kg, –0.4 kg; p&lt;0.01] and –2.0 kg [–2.8 kg, –1.2 kg; p&lt;0.001], respectively), but not for oral semaglutide 3 mg (ETD [95% CI] –0.0 kg [–0.9 kg, 0.8 kg; not significant]). Similar reductions in HbA1c and body weight were observed in the Chinese subpopulation, which represented 74.9% of participants in the overall population. Adverse events (AEs) occurred in between 65.4% and 72.3% of participants receiving oral semaglutide (for all doses) and 57.3% of participants with placebo. Most AEs were mild to moderate in severity, with few serious AEs reported; the most commonly reported AEs were gastrointestinal-related and were more frequent with semaglutide (all doses) than with placebo. The proportion of AEs was slightly higher in the Chinese subpopulation. Conclusions/interpretation: Oral semaglutide resulted in significantly greater reductions in HbA1c across all doses and in significant body weight reductions for the 7 mg and 14 mg doses when compared with placebo in predominantly Chinese participants with type 2 diabetes insufficiently controlled by diet and exercise alone. Oral semaglutide was generally well tolerated, with a safety profile consistent with that seen in the global PIONEER trials. Trial registration: ClinicalTrials.gov NCT04109547. Funding: Novo Nordisk A/S. 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spelling v2 67735 2024-09-19 Efficacy and safety of oral semaglutide monotherapy vs placebo in a predominantly Chinese population with type 2 diabetes (PIONEER 11): a double-blind, Phase IIIa, randomised trial 5399f4c6e6a70f3608a084ddb938511a 0000-0001-8519-4964 Steve Bain Steve Bain true false 2024-09-19 MEDS Aims/hypothesis: The aim of this study was to evaluate the efficacy and safety of oral semaglutide monotherapy vs placebo in a predominantly Chinese population with type 2 diabetes insufficiently controlled with diet and exercise alone. Methods: The Peptide Innovation for Early Diabetes Treatment (PIONEER) 11 trial was a double-blind, randomised, Phase IIIa trial conducted across 52 sites in the China region (mainland China and Taiwan), Hungary, Serbia and Ukraine. Eligible participants were ≥18 years (≥20 years in Taiwan), had a diagnosis of type 2 diabetes with HbA1c 53–86 mmol/mol (7.0–10.0%) and were not receiving any glucose-lowering drugs. After a 4-week run-in period in which participants were treated with diet and exercise alone, those who fulfilled the randomisation criteria were randomised (1:1:1:1) using a web-based randomisation system to receive once-daily oral semaglutide 3 mg, 7 mg or 14 mg or placebo for 26 weeks (using a 4-week dose-escalation regimen for the higher doses). Randomisation was stratified according to whether participants were from the China region or elsewhere. The primary and confirmatory secondary endpoints were change from baseline to week 26 in HbA1c and body weight (kg), respectively. Safety was assessed in all participants exposed to at least one dose of the trial product. Results: Between October 2019 and October 2021, a total of 774 participants were screened and 521 participants were randomised to oral semaglutide 3 mg (n=130), 7 mg (n=130), 14 mg (n=130) or placebo (n=131); most participants (92.5%, n=482) completed the trial, with 39 participants prematurely discontinuing treatment. The number of participants contributing to the trial analyses was based on the total number of participants who were randomised at the beginning of the trial. The majority of participants were male (63.7%), and the mean age of participants was 52 years. At baseline, mean HbA1c and body weight were 63 mmol/mol (8.0%) and 79.6 kg, respectively. Oral semaglutide resulted in significantly greater reductions in HbA1c than placebo at week 26 (p<0.001 for all doses). The estimated treatment differences (ETDs [95% CIs]) for oral semaglutide 3 mg, 7 mg and 14 mg vs placebo were –11 (–13, –9) mmol/mol, –16 (–18, –13) mmol/mol and –17 (–19, –15) mmol/mol, respectively. The corresponding ETDs in percentage points (95% CI) vs placebo were –1.0 (–1.2, –0.8), –1.4 (–1.6, –1.2) and –1.5 (–1.8, –1.3), respectively. Significantly greater reductions in body weight were also observed for oral semaglutide 7 mg and 14 mg than for placebo at week 26 (ETD [95% CI] –1.2 kg [–2.0 kg, –0.4 kg; p<0.01] and –2.0 kg [–2.8 kg, –1.2 kg; p<0.001], respectively), but not for oral semaglutide 3 mg (ETD [95% CI] –0.0 kg [–0.9 kg, 0.8 kg; not significant]). Similar reductions in HbA1c and body weight were observed in the Chinese subpopulation, which represented 74.9% of participants in the overall population. Adverse events (AEs) occurred in between 65.4% and 72.3% of participants receiving oral semaglutide (for all doses) and 57.3% of participants with placebo. Most AEs were mild to moderate in severity, with few serious AEs reported; the most commonly reported AEs were gastrointestinal-related and were more frequent with semaglutide (all doses) than with placebo. The proportion of AEs was slightly higher in the Chinese subpopulation. Conclusions/interpretation: Oral semaglutide resulted in significantly greater reductions in HbA1c across all doses and in significant body weight reductions for the 7 mg and 14 mg doses when compared with placebo in predominantly Chinese participants with type 2 diabetes insufficiently controlled by diet and exercise alone. Oral semaglutide was generally well tolerated, with a safety profile consistent with that seen in the global PIONEER trials. Trial registration: ClinicalTrials.gov NCT04109547. Funding: Novo Nordisk A/S. Graphical Abstract: Journal Article Diabetologia 67 1783 1799 Springer Nature 0012-186X 1432-0428 China, GLP-1 analogue, Glycaemic control, Incretin therapy, Phase III, Semaglutide, Type 2 diabetes 1 9 2024 2024-09-01 10.1007/s00125-024-06142-3 COLLEGE NANME Medical School COLLEGE CODE MEDS Swansea University This trial was funded by Novo Nordisk A/S, Søborg, Denmark. The study sponsor was involved in the study design, data collection, analysis and interpretation and the writing of this report. 2024-09-19T15:56:23.9889304 2024-09-19T13:51:23.7796135 Faculty of Medicine, Health and Life Sciences Swansea University Medical School - Biomedical Science Weiqing Wang 0000-0001-6027-3084 1 Steve Bain 0000-0001-8519-4964 2 Fang Bian 0009-0005-1219-4345 3 Rui Chen 0009-0007-3128-3524 4 Sanaz Gabery 0000-0002-2243-7540 5 Shan Huang 0000-0001-8125-953X 6 Thomas B. Jensen 0000-0002-8920-9374 7 Bifen Luo 0000-0001-7166-278X 8 Guoyue Yuan 0000-0003-0822-6066 9 Guang Ning 0000-0002-5754-7635 10 67735__31390__bb128ea276794a5c8f92781a1703a606.pdf 67735.VOR.pdf 2024-09-19T14:28:06.2397901 Output 1442569 application/pdf Version of Record true © The Author(s) 2024. This article is licensed under a Creative Commons Attribution 4.0 International License (CC-BY 4.0). true eng http://creativecommons.org/licenses/by/4.0/
title Efficacy and safety of oral semaglutide monotherapy vs placebo in a predominantly Chinese population with type 2 diabetes (PIONEER 11): a double-blind, Phase IIIa, randomised trial
spellingShingle Efficacy and safety of oral semaglutide monotherapy vs placebo in a predominantly Chinese population with type 2 diabetes (PIONEER 11): a double-blind, Phase IIIa, randomised trial
Steve Bain
title_short Efficacy and safety of oral semaglutide monotherapy vs placebo in a predominantly Chinese population with type 2 diabetes (PIONEER 11): a double-blind, Phase IIIa, randomised trial
title_full Efficacy and safety of oral semaglutide monotherapy vs placebo in a predominantly Chinese population with type 2 diabetes (PIONEER 11): a double-blind, Phase IIIa, randomised trial
title_fullStr Efficacy and safety of oral semaglutide monotherapy vs placebo in a predominantly Chinese population with type 2 diabetes (PIONEER 11): a double-blind, Phase IIIa, randomised trial
title_full_unstemmed Efficacy and safety of oral semaglutide monotherapy vs placebo in a predominantly Chinese population with type 2 diabetes (PIONEER 11): a double-blind, Phase IIIa, randomised trial
title_sort Efficacy and safety of oral semaglutide monotherapy vs placebo in a predominantly Chinese population with type 2 diabetes (PIONEER 11): a double-blind, Phase IIIa, randomised trial
author_id_str_mv 5399f4c6e6a70f3608a084ddb938511a
author_id_fullname_str_mv 5399f4c6e6a70f3608a084ddb938511a_***_Steve Bain
author Steve Bain
author2 Weiqing Wang
Steve Bain
Fang Bian
Rui Chen
Sanaz Gabery
Shan Huang
Thomas B. Jensen
Bifen Luo
Guoyue Yuan
Guang Ning
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container_title Diabetologia
container_volume 67
container_start_page 1783
publishDate 2024
institution Swansea University
issn 0012-186X
1432-0428
doi_str_mv 10.1007/s00125-024-06142-3
publisher Springer Nature
college_str Faculty of Medicine, Health and Life Sciences
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hierarchy_top_title Faculty of Medicine, Health and Life Sciences
hierarchy_parent_id facultyofmedicinehealthandlifesciences
hierarchy_parent_title Faculty of Medicine, Health and Life Sciences
department_str Swansea University Medical School - Biomedical Science{{{_:::_}}}Faculty of Medicine, Health and Life Sciences{{{_:::_}}}Swansea University Medical School - Biomedical Science
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description Aims/hypothesis: The aim of this study was to evaluate the efficacy and safety of oral semaglutide monotherapy vs placebo in a predominantly Chinese population with type 2 diabetes insufficiently controlled with diet and exercise alone. Methods: The Peptide Innovation for Early Diabetes Treatment (PIONEER) 11 trial was a double-blind, randomised, Phase IIIa trial conducted across 52 sites in the China region (mainland China and Taiwan), Hungary, Serbia and Ukraine. Eligible participants were ≥18 years (≥20 years in Taiwan), had a diagnosis of type 2 diabetes with HbA1c 53–86 mmol/mol (7.0–10.0%) and were not receiving any glucose-lowering drugs. After a 4-week run-in period in which participants were treated with diet and exercise alone, those who fulfilled the randomisation criteria were randomised (1:1:1:1) using a web-based randomisation system to receive once-daily oral semaglutide 3 mg, 7 mg or 14 mg or placebo for 26 weeks (using a 4-week dose-escalation regimen for the higher doses). Randomisation was stratified according to whether participants were from the China region or elsewhere. The primary and confirmatory secondary endpoints were change from baseline to week 26 in HbA1c and body weight (kg), respectively. Safety was assessed in all participants exposed to at least one dose of the trial product. Results: Between October 2019 and October 2021, a total of 774 participants were screened and 521 participants were randomised to oral semaglutide 3 mg (n=130), 7 mg (n=130), 14 mg (n=130) or placebo (n=131); most participants (92.5%, n=482) completed the trial, with 39 participants prematurely discontinuing treatment. The number of participants contributing to the trial analyses was based on the total number of participants who were randomised at the beginning of the trial. The majority of participants were male (63.7%), and the mean age of participants was 52 years. At baseline, mean HbA1c and body weight were 63 mmol/mol (8.0%) and 79.6 kg, respectively. Oral semaglutide resulted in significantly greater reductions in HbA1c than placebo at week 26 (p<0.001 for all doses). The estimated treatment differences (ETDs [95% CIs]) for oral semaglutide 3 mg, 7 mg and 14 mg vs placebo were –11 (–13, –9) mmol/mol, –16 (–18, –13) mmol/mol and –17 (–19, –15) mmol/mol, respectively. The corresponding ETDs in percentage points (95% CI) vs placebo were –1.0 (–1.2, –0.8), –1.4 (–1.6, –1.2) and –1.5 (–1.8, –1.3), respectively. Significantly greater reductions in body weight were also observed for oral semaglutide 7 mg and 14 mg than for placebo at week 26 (ETD [95% CI] –1.2 kg [–2.0 kg, –0.4 kg; p<0.01] and –2.0 kg [–2.8 kg, –1.2 kg; p<0.001], respectively), but not for oral semaglutide 3 mg (ETD [95% CI] –0.0 kg [–0.9 kg, 0.8 kg; not significant]). Similar reductions in HbA1c and body weight were observed in the Chinese subpopulation, which represented 74.9% of participants in the overall population. Adverse events (AEs) occurred in between 65.4% and 72.3% of participants receiving oral semaglutide (for all doses) and 57.3% of participants with placebo. Most AEs were mild to moderate in severity, with few serious AEs reported; the most commonly reported AEs were gastrointestinal-related and were more frequent with semaglutide (all doses) than with placebo. The proportion of AEs was slightly higher in the Chinese subpopulation. Conclusions/interpretation: Oral semaglutide resulted in significantly greater reductions in HbA1c across all doses and in significant body weight reductions for the 7 mg and 14 mg doses when compared with placebo in predominantly Chinese participants with type 2 diabetes insufficiently controlled by diet and exercise alone. Oral semaglutide was generally well tolerated, with a safety profile consistent with that seen in the global PIONEER trials. Trial registration: ClinicalTrials.gov NCT04109547. Funding: Novo Nordisk A/S. Graphical Abstract:
published_date 2024-09-01T15:56:23Z
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