PIONEER REAL UK: A Multi-Centre, Prospective, Real-World Study of Once-Daily Oral Semaglutide Use in Adults with Type 2 Diabetes.

INTRODUCTION: Oral semaglutide provides an alternative to injectable glucagon-like peptide-1 receptor agonists (GLP-1RAs) for treatment of type 2 diabetes (T2D). The PIONEER REAL studies evaluate clinical outcomes of oral semaglutide treatment of T2D in a real-world setting. PIONEER REAL UK focused on adults living with T2D in the UK. METHODS: The multi-centre, prospective and non-interventional single-arm study enrolled 333 participants and followed them for 34-44 weeks. Participants were treated as part of routine clinical practice and had not been previously treated with injectable glucose-lowering medication. The primary endpoint was change in glycated haemoglobin (HbA) from baseline to end of study (EOS). Secondary endpoints included change in body weight, proportion of participants with HbA < 7% (53 mmol/mol) at EOS and proportion of participants with ≥ 1%-point HbA reduction and body weight reduction of ≥ 3% or ≥ 5% at EOS. Treatment satisfaction was assessed by Diabetes Treatment Satisfaction Questionnaire (DTSQ) status and change. RESULTS: Of 333 participants, 299 completed the study and 227 were on treatment at EOS. People treated with oral semaglutide experienced significantly reduced HbA by an estimated change of - 1.1%-points (95% CI - 1.27 to - 0.96; P < 0.0001) or - 12.2 mmol/mol (CI - 13.87 to - 10.47; P < 0.0001). Estimated change in body weight was - 4.8 kg (CI - 5.47 to - 4.12; P < 0.0001). At EOS, an HbA level < 7% (53 mmol/mol) was recorded in 46.3% of participants. A ≥ 1%-point reduction in HbA combined with a ≥ 3% reduction in body weight was observed in 36.4% of participants, and 27.1% had a ≥ 1%-point reduction in HbA and a ≥ 5% body weight reduction. Treatment satisfaction improved significantly during the study. No new safety concerns or cases of severe hypoglycaemia were reported. CONCLUSION: People living with T2D in the UK experienced a meaningful decrease in HbA and body weight after initiation of oral semaglutide treatment. No new safety issues were observed. TRIAL REGISTRATION: ClinicalTrials.gov: NCT04862923. Graphical plain language summary available for this article.