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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, Volume: 67, Pages: 1800 - 1816

Swansea University Author: Steve Bain Orcid Logo

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

Abstract

Aims/hypothesis: The 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. Methods: The Peptide Innovation for Early Diabetes Treatment (PIONEER) 12 trial...

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Published in: Diabetologia
ISSN: 0012-186X 1432-0428
Published: Springer Science and Business Media LLC 2024
Online Access: Check full text

URI: https://cronfa.swan.ac.uk/Record/cronfa66544
Abstract: Aims/hypothesis: The 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. Methods: The 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). Results: Of 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/interpretation: Significantly 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 registration: ClinicalTrials.gov NCT04017832.
Keywords: GLP-1 analogue; Glycaemic control; Incretin therapy; Phase III; Semaglutide; Type 2 diabetes
College: Faculty of Medicine, Health and Life Sciences
Funders: Novo Nordisk A/S
Start Page: 1800
End Page: 1816

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