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

• Published in: Diabetologia 2024-09, Vol.67 (9), p.1783-1799
• Main Authors: Wang, Weiqing, Bain, Stephen C., Bian, Fang, Chen, Rui, Gabery, Sanaz, Huang, Shan, Jensen, Thomas B., Luo, Bifen, Yuan, Guoyue, Ning, Guang
• Format: Article
• Language: English
• Subjects: Administration, Oral; Adult; Aged; Asian People; Blood Glucose - drug effects; Body weight; China; Diabetes; Diabetes mellitus (non-insulin dependent); Diabetes Mellitus, Type 2 - blood; Diabetes Mellitus, Type 2 - drug therapy; Diet; Double-Blind Method; East Asian People; Female; Glucagon-Like Peptides - administration & dosage; Glucagon-Like Peptides - adverse effects; Glucagon-Like Peptides - therapeutic use; Glycated Hemoglobin - metabolism; Human Physiology; Humans; Hypoglycemic Agents - administration & dosage; Hypoglycemic Agents - adverse effects; Hypoglycemic Agents - therapeutic use; Internal Medicine; Male; Medicine; Medicine & Public Health; Metabolic Diseases; Middle Aged; Placebos; Population studies; Treatment Outcome
• ISSN: 0012-186X; 1432-0428; 1432-0428
• DOI: 10.1007/s00125-024-06142-3

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 HbA 1c 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 HbA 1c 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 HbA 1c and body weight were 63 mmol/mol (8.0%) and 79.6 kg, respectively. Oral semaglutide resulted in significantly greater reductions in HbA 1c than placebo at week 26 ( p