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Efficacy and safety of oral semaglutide vs sitagliptin in a predominantly Chinese population with type 2 diabetes uncontrolled with metformin: PIONEER 12, a double-blind, Phase IIIa, randomised trial

Linong Ji Orcid Logo, Rikke M. Agesen Orcid Logo, Steve Bain Orcid Logo, Fangming Fu Orcid Logo, Sanaz Gabery Orcid Logo, Jianlin Geng Orcid Logo, Yiming Li Orcid Logo, Yibing Lu, Bifen Luo Orcid Logo, Wuyan Pang, Yi Tao Orcid Logo, (for the PIONEER 12 investigators)

Diabetologia

Swansea University Author: Steve Bain Orcid Logo

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DOI (Published version): 10.1007/s00125-024-06133-4

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Aims/hypothesisThe aim of this study was to assess the efficacy and safety of oral semaglutide vs sitagliptin in a predominantly Chinese population with type 2 diabetes inadequately controlled with metformin treatment.MethodsThe Peptide Innovation for Early Diabetes Treatment (PIONEER) 12 trial was...

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Published in: Diabetologia
ISSN: 0012-186X 1432-0428
Published: Springer Science and Business Media LLC 2024
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URI: https://cronfa.swan.ac.uk/Record/cronfa66544
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fullrecord <?xml version="1.0" encoding="utf-8"?><rfc1807 xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xmlns:xsd="http://www.w3.org/2001/XMLSchema"><bib-version>v2</bib-version><id>66544</id><entry>2024-05-31</entry><title>Efficacy and safety of oral semaglutide vs sitagliptin in a predominantly Chinese population with type 2 diabetes uncontrolled with metformin: PIONEER 12, a double-blind, Phase IIIa, randomised trial</title><swanseaauthors><author><sid>5399f4c6e6a70f3608a084ddb938511a</sid><ORCID>0000-0001-8519-4964</ORCID><firstname>Steve</firstname><surname>Bain</surname><name>Steve Bain</name><active>true</active><ethesisStudent>false</ethesisStudent></author></swanseaauthors><date>2024-05-31</date><deptcode>MEDS</deptcode><abstract>Aims/hypothesisThe aim of this study was to assess the efficacy and safety of oral semaglutide vs sitagliptin in a predominantly Chinese population with type 2 diabetes inadequately controlled with metformin treatment.MethodsThe Peptide Innovation for Early Diabetes Treatment (PIONEER) 12 trial was a randomised, double-dummy, active-controlled, parallel-group, Phase IIIa trial conducted over 26 weeks at 90 sites across the China region (including mainland China, Taiwan and Hong Kong) and five other countries. Adults aged ≥18 years (≥20 years in Taiwan) with a diagnosis of type 2 diabetes, HbA1c between 53 and 91 mmol/mol (inclusive) and treated with a stable daily dose of metformin were eligible for inclusion. Participants were randomised (1:1:1:1) using a web-based randomisation system to either once-daily oral semaglutide (3 mg, 7 mg or 14 mg) or once-daily oral sitagliptin 100 mg. Treatment allocation was masked to both participants and investigators. Randomisation was stratified according to whether participants were from the China region or elsewhere. The primary endpoint was change in HbA1c from baseline to week 26. The confirmatory secondary endpoint was change in body weight (kg) from baseline to week 26. All randomised participants were included in the full analysis set (FAS). All participants exposed to at least one dose of trial product were included in the safety analysis (SAS).ResultsOf 1839 participants screened, 1441 were randomly assigned to oral semaglutide 3 mg (n=361), 7 mg (n=360), 14 mg (n=361) or sitagliptin 100 mg (n=359) and included in the FAS. A total of 1438 participants were included in the SAS. In total, 75.2% of participants were from the China region. A total of 1372 (95.2%) participants completed the trial and 130 participants prematurely discontinued treatment (8.3%, 8.6% and 15.0% for oral semaglutide 3 mg, 7 mg and 14 mg, respectively; 4.2% for sitagliptin 100 mg). Significantly greater reductions in HbA1c from baseline to week 26 were reported for all doses of oral semaglutide vs sitagliptin 100 mg. For oral semaglutide 3 mg, 7 mg and 14 mg vs sitagliptin 100 mg, the estimated treatment differences (ETDs [95% CI]) were –2 (–4, –1) mmol/mol, –8 (–9, –6) mmol/mol and –11 (–12, –9) mmol/mol, respectively. The corresponding ETDs (95% CI) in percentage points vs sitagliptin 100 mg were –0.2 (–0.3, –0.1), –0.7 (–0.8, –0.6) and –1.0 (–1.1, –0.8), respectively. Reductions in body weight were significantly greater for all doses of oral semaglutide vs sitagliptin 100 mg (ETD [95% CI] –0.9 [–1.4, –0.4] kg, –2.3 [–2.8, –1.8] kg and –3.3 [–3.8, –2.8] kg for 3 mg, 7 mg and 14 mg, respectively). In the subpopulation of participants from the China region (75.2% of trial participants), reductions in HbA1c and body weight from baseline to week 26 were similar to those seen in the overall population. The most frequent adverse events in the semaglutide treatment arms were gastrointestinal, although these were mostly transient and mild/moderate in severity.Conclusions/interpretationSignificantly greater reductions in both HbA1c and body weight over 26 weeks were seen with oral semaglutide 3 mg, 7 mg and 14 mg than with sitagliptin 100 mg in a predominantly Chinese population with type 2 diabetes inadequately controlled with metformin treatment. Oral semaglutide was generally well tolerated, with a safety profile consistent with that seen in the global PIONEER trials.Trial registrationClinicalTrials.gov NCT04017832.</abstract><type>Journal Article</type><journal>Diabetologia</journal><volume>0</volume><journalNumber/><paginationStart/><paginationEnd/><publisher>Springer Science and Business Media LLC</publisher><placeOfPublication/><isbnPrint/><isbnElectronic/><issnPrint>0012-186X</issnPrint><issnElectronic>1432-0428</issnElectronic><keywords>GLP-1 analogue; Glycaemic control; Incretin therapy; Phase III; Semaglutide; Type 2 diabetes</keywords><publishedDay>10</publishedDay><publishedMonth>7</publishedMonth><publishedYear>2024</publishedYear><publishedDate>2024-07-10</publishedDate><doi>10.1007/s00125-024-06133-4</doi><url/><notes/><college>COLLEGE NANME</college><department>Medical School</department><CollegeCode>COLLEGE CODE</CollegeCode><DepartmentCode>MEDS</DepartmentCode><institution>Swansea University</institution><apcterm>SU Library paid the OA fee (TA Institutional Deal)</apcterm><funders>Novo Nordisk A/S</funders><projectreference/><lastEdited>2024-08-01T11:24:40.5140769</lastEdited><Created>2024-05-31T11:18:59.3301620</Created><path><level id="1">Faculty of Medicine, Health and Life Sciences</level><level id="2">Swansea University Medical School - Biomedical Science</level></path><authors><author><firstname>Linong</firstname><surname>Ji</surname><orcid>0000-0002-3262-2168</orcid><order>1</order></author><author><firstname>Rikke M.</firstname><surname>Agesen</surname><orcid>0000-0002-7649-7928</orcid><order>2</order></author><author><firstname>Steve</firstname><surname>Bain</surname><orcid>0000-0001-8519-4964</orcid><order>3</order></author><author><firstname>Fangming</firstname><surname>Fu</surname><orcid>0000-0002-0874-7526</orcid><order>4</order></author><author><firstname>Sanaz</firstname><surname>Gabery</surname><orcid>0000-0002-2243-7540</orcid><order>5</order></author><author><firstname>Jianlin</firstname><surname>Geng</surname><orcid>0009-0001-6844-9221</orcid><order>6</order></author><author><firstname>Yiming</firstname><surname>Li</surname><orcid>0000-0002-1828-8765</orcid><order>7</order></author><author><firstname>Yibing</firstname><surname>Lu</surname><order>8</order></author><author><firstname>Bifen</firstname><surname>Luo</surname><orcid>0000-0001-7166-278x</orcid><order>9</order></author><author><firstname>Wuyan</firstname><surname>Pang</surname><order>10</order></author><author><firstname>Yi</firstname><surname>Tao</surname><orcid>0009-0003-6453-5354</orcid><order>11</order></author><author><firstname>(for the PIONEER 12</firstname><surname>investigators)</surname><order>12</order></author></authors><documents><document><filename>66544__31020__1119d26004a4496b8f6846c61d140347.pdf</filename><originalFilename>66544.VoR.pdf</originalFilename><uploaded>2024-08-01T11:22:41.4049014</uploaded><type>Output</type><contentLength>1522886</contentLength><contentType>application/pdf</contentType><version>Version of Record</version><cronfaStatus>true</cronfaStatus><documentNotes>© The Author(s) 2024. 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spelling v2 66544 2024-05-31 Efficacy and safety of oral semaglutide vs sitagliptin in a predominantly Chinese population with type 2 diabetes uncontrolled with metformin: PIONEER 12, a double-blind, Phase IIIa, randomised trial 5399f4c6e6a70f3608a084ddb938511a 0000-0001-8519-4964 Steve Bain Steve Bain true false 2024-05-31 MEDS Aims/hypothesisThe aim of this study was to assess the efficacy and safety of oral semaglutide vs sitagliptin in a predominantly Chinese population with type 2 diabetes inadequately controlled with metformin treatment.MethodsThe Peptide Innovation for Early Diabetes Treatment (PIONEER) 12 trial was a randomised, double-dummy, active-controlled, parallel-group, Phase IIIa trial conducted over 26 weeks at 90 sites across the China region (including mainland China, Taiwan and Hong Kong) and five other countries. Adults aged ≥18 years (≥20 years in Taiwan) with a diagnosis of type 2 diabetes, HbA1c between 53 and 91 mmol/mol (inclusive) and treated with a stable daily dose of metformin were eligible for inclusion. Participants were randomised (1:1:1:1) using a web-based randomisation system to either once-daily oral semaglutide (3 mg, 7 mg or 14 mg) or once-daily oral sitagliptin 100 mg. Treatment allocation was masked to both participants and investigators. Randomisation was stratified according to whether participants were from the China region or elsewhere. The primary endpoint was change in HbA1c from baseline to week 26. The confirmatory secondary endpoint was change in body weight (kg) from baseline to week 26. All randomised participants were included in the full analysis set (FAS). All participants exposed to at least one dose of trial product were included in the safety analysis (SAS).ResultsOf 1839 participants screened, 1441 were randomly assigned to oral semaglutide 3 mg (n=361), 7 mg (n=360), 14 mg (n=361) or sitagliptin 100 mg (n=359) and included in the FAS. A total of 1438 participants were included in the SAS. In total, 75.2% of participants were from the China region. A total of 1372 (95.2%) participants completed the trial and 130 participants prematurely discontinued treatment (8.3%, 8.6% and 15.0% for oral semaglutide 3 mg, 7 mg and 14 mg, respectively; 4.2% for sitagliptin 100 mg). Significantly greater reductions in HbA1c from baseline to week 26 were reported for all doses of oral semaglutide vs sitagliptin 100 mg. For oral semaglutide 3 mg, 7 mg and 14 mg vs sitagliptin 100 mg, the estimated treatment differences (ETDs [95% CI]) were –2 (–4, –1) mmol/mol, –8 (–9, –6) mmol/mol and –11 (–12, –9) mmol/mol, respectively. The corresponding ETDs (95% CI) in percentage points vs sitagliptin 100 mg were –0.2 (–0.3, –0.1), –0.7 (–0.8, –0.6) and –1.0 (–1.1, –0.8), respectively. Reductions in body weight were significantly greater for all doses of oral semaglutide vs sitagliptin 100 mg (ETD [95% CI] –0.9 [–1.4, –0.4] kg, –2.3 [–2.8, –1.8] kg and –3.3 [–3.8, –2.8] kg for 3 mg, 7 mg and 14 mg, respectively). In the subpopulation of participants from the China region (75.2% of trial participants), reductions in HbA1c and body weight from baseline to week 26 were similar to those seen in the overall population. The most frequent adverse events in the semaglutide treatment arms were gastrointestinal, although these were mostly transient and mild/moderate in severity.Conclusions/interpretationSignificantly greater reductions in both HbA1c and body weight over 26 weeks were seen with oral semaglutide 3 mg, 7 mg and 14 mg than with sitagliptin 100 mg in a predominantly Chinese population with type 2 diabetes inadequately controlled with metformin treatment. Oral semaglutide was generally well tolerated, with a safety profile consistent with that seen in the global PIONEER trials.Trial registrationClinicalTrials.gov NCT04017832. Journal Article Diabetologia 0 Springer Science and Business Media LLC 0012-186X 1432-0428 GLP-1 analogue; Glycaemic control; Incretin therapy; Phase III; Semaglutide; Type 2 diabetes 10 7 2024 2024-07-10 10.1007/s00125-024-06133-4 COLLEGE NANME Medical School COLLEGE CODE MEDS Swansea University SU Library paid the OA fee (TA Institutional Deal) Novo Nordisk A/S 2024-08-01T11:24:40.5140769 2024-05-31T11:18:59.3301620 Faculty of Medicine, Health and Life Sciences Swansea University Medical School - Biomedical Science Linong Ji 0000-0002-3262-2168 1 Rikke M. Agesen 0000-0002-7649-7928 2 Steve Bain 0000-0001-8519-4964 3 Fangming Fu 0000-0002-0874-7526 4 Sanaz Gabery 0000-0002-2243-7540 5 Jianlin Geng 0009-0001-6844-9221 6 Yiming Li 0000-0002-1828-8765 7 Yibing Lu 8 Bifen Luo 0000-0001-7166-278x 9 Wuyan Pang 10 Yi Tao 0009-0003-6453-5354 11 (for the PIONEER 12 investigators) 12 66544__31020__1119d26004a4496b8f6846c61d140347.pdf 66544.VoR.pdf 2024-08-01T11:22:41.4049014 Output 1522886 application/pdf Version of Record true © The Author(s) 2024. This article is licensed under a Creative Commons Attribution 4.0 International License. true eng http://creativecommons.org/licenses/by/4.0/
title Efficacy and safety of oral semaglutide vs sitagliptin in a predominantly Chinese population with type 2 diabetes uncontrolled with metformin: PIONEER 12, a double-blind, Phase IIIa, randomised trial
spellingShingle Efficacy and safety of oral semaglutide vs sitagliptin in a predominantly Chinese population with type 2 diabetes uncontrolled with metformin: PIONEER 12, a double-blind, Phase IIIa, randomised trial
Steve Bain
title_short Efficacy and safety of oral semaglutide vs sitagliptin in a predominantly Chinese population with type 2 diabetes uncontrolled with metformin: PIONEER 12, a double-blind, Phase IIIa, randomised trial
title_full Efficacy and safety of oral semaglutide vs sitagliptin in a predominantly Chinese population with type 2 diabetes uncontrolled with metformin: PIONEER 12, a double-blind, Phase IIIa, randomised trial
title_fullStr Efficacy and safety of oral semaglutide vs sitagliptin in a predominantly Chinese population with type 2 diabetes uncontrolled with metformin: PIONEER 12, a double-blind, Phase IIIa, randomised trial
title_full_unstemmed Efficacy and safety of oral semaglutide vs sitagliptin in a predominantly Chinese population with type 2 diabetes uncontrolled with metformin: PIONEER 12, a double-blind, Phase IIIa, randomised trial
title_sort Efficacy and safety of oral semaglutide vs sitagliptin in a predominantly Chinese population with type 2 diabetes uncontrolled with metformin: PIONEER 12, a double-blind, Phase IIIa, randomised trial
author_id_str_mv 5399f4c6e6a70f3608a084ddb938511a
author_id_fullname_str_mv 5399f4c6e6a70f3608a084ddb938511a_***_Steve Bain
author Steve Bain
author2 Linong Ji
Rikke M. Agesen
Steve Bain
Fangming Fu
Sanaz Gabery
Jianlin Geng
Yiming Li
Yibing Lu
Bifen Luo
Wuyan Pang
Yi Tao
(for the PIONEER 12 investigators)
format Journal article
container_title Diabetologia
container_volume 0
publishDate 2024
institution Swansea University
issn 0012-186X
1432-0428
doi_str_mv 10.1007/s00125-024-06133-4
publisher Springer Science and Business Media LLC
college_str Faculty of Medicine, Health and Life Sciences
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hierarchy_top_id facultyofmedicinehealthandlifesciences
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
document_store_str 1
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description Aims/hypothesisThe aim of this study was to assess the efficacy and safety of oral semaglutide vs sitagliptin in a predominantly Chinese population with type 2 diabetes inadequately controlled with metformin treatment.MethodsThe Peptide Innovation for Early Diabetes Treatment (PIONEER) 12 trial was a randomised, double-dummy, active-controlled, parallel-group, Phase IIIa trial conducted over 26 weeks at 90 sites across the China region (including mainland China, Taiwan and Hong Kong) and five other countries. Adults aged ≥18 years (≥20 years in Taiwan) with a diagnosis of type 2 diabetes, HbA1c between 53 and 91 mmol/mol (inclusive) and treated with a stable daily dose of metformin were eligible for inclusion. Participants were randomised (1:1:1:1) using a web-based randomisation system to either once-daily oral semaglutide (3 mg, 7 mg or 14 mg) or once-daily oral sitagliptin 100 mg. Treatment allocation was masked to both participants and investigators. Randomisation was stratified according to whether participants were from the China region or elsewhere. The primary endpoint was change in HbA1c from baseline to week 26. The confirmatory secondary endpoint was change in body weight (kg) from baseline to week 26. All randomised participants were included in the full analysis set (FAS). All participants exposed to at least one dose of trial product were included in the safety analysis (SAS).ResultsOf 1839 participants screened, 1441 were randomly assigned to oral semaglutide 3 mg (n=361), 7 mg (n=360), 14 mg (n=361) or sitagliptin 100 mg (n=359) and included in the FAS. A total of 1438 participants were included in the SAS. In total, 75.2% of participants were from the China region. A total of 1372 (95.2%) participants completed the trial and 130 participants prematurely discontinued treatment (8.3%, 8.6% and 15.0% for oral semaglutide 3 mg, 7 mg and 14 mg, respectively; 4.2% for sitagliptin 100 mg). Significantly greater reductions in HbA1c from baseline to week 26 were reported for all doses of oral semaglutide vs sitagliptin 100 mg. For oral semaglutide 3 mg, 7 mg and 14 mg vs sitagliptin 100 mg, the estimated treatment differences (ETDs [95% CI]) were –2 (–4, –1) mmol/mol, –8 (–9, –6) mmol/mol and –11 (–12, –9) mmol/mol, respectively. The corresponding ETDs (95% CI) in percentage points vs sitagliptin 100 mg were –0.2 (–0.3, –0.1), –0.7 (–0.8, –0.6) and –1.0 (–1.1, –0.8), respectively. Reductions in body weight were significantly greater for all doses of oral semaglutide vs sitagliptin 100 mg (ETD [95% CI] –0.9 [–1.4, –0.4] kg, –2.3 [–2.8, –1.8] kg and –3.3 [–3.8, –2.8] kg for 3 mg, 7 mg and 14 mg, respectively). In the subpopulation of participants from the China region (75.2% of trial participants), reductions in HbA1c and body weight from baseline to week 26 were similar to those seen in the overall population. The most frequent adverse events in the semaglutide treatment arms were gastrointestinal, although these were mostly transient and mild/moderate in severity.Conclusions/interpretationSignificantly greater reductions in both HbA1c and body weight over 26 weeks were seen with oral semaglutide 3 mg, 7 mg and 14 mg than with sitagliptin 100 mg in a predominantly Chinese population with type 2 diabetes inadequately controlled with metformin treatment. Oral semaglutide was generally well tolerated, with a safety profile consistent with that seen in the global PIONEER trials.Trial registrationClinicalTrials.gov NCT04017832.
published_date 2024-07-10T11:24:41Z
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