Oral Semaglutide Use in Type 2 Diabetes: A Pooled Analysis of Clinical and Patient-Reported Outcomes from Seven PIONEER REAL Prospective Real-World Studies

Introduction: Oral semaglutide is a glucagon-like peptide 1 receptor agonist (GLP-1RA) approved for improving glycemic control in adults with type 2 diabetes (T2D). The PIONEER REAL program evaluates clinical and patient-reported outcomes of oral semaglutide treatment as part of routine clinical practice across 13 countries. Here, data from Canada, Denmark, Italy, the Netherlands, Sweden, Switzerland, and the UK are pooled and analyzed to address treatment satisfaction as well as glycated hemoglobin (HbA(1C)) and body weight changes in relevant subgroup analyses. Methods: This pooled analysis encompasses seven country-specific, non-interventional, multicenter, phase 4, prospective, single-arm clinical studies assessing the use of oral semaglutide in adults with T2D. Primary endpoint was the change in HbA(1C) from baseline to end of study (EOS), and secondary endpoints included changes in body weight and treatment satisfaction. For the analyses, results were stratified by age, T2D duration, and oral semaglutide dose at EOS as well as baseline HbA(1C), body weight, and body mass index. Results: Oral semaglutide treatment was initiated by 1615 participants. At EOS, 1222 (76%) participants out of the 1483 (92%) who completed the study were on treatment. Estimated changes in HbA(1C) and body weight from baseline to week 38 were - 1.0%-point (95% CI - 1.08 to - 0.97; P < 0.0001) and - 5.0% (CI - 5.37 to - 4.72; P < 0.0001). Treatment satisfaction increased significantly during the study. Shorter T2D duration interacted with higher HbA(1C) reduction and body weight loss. Interaction was also observed between higher baseline HbA(1C) and more pronounced decrease in HbA(1C). No significant interactions were detected between clinical outcomes and age or physician setting. Conclusion: The PIONEER REAL pooled analysis shows that people initiating oral semaglutide treatment experience improved glycemic control and body weight loss across age groups and T2D duration. This occurs regardless of specialist or primary care practice setting and is accompanied by an increased treatment satisfaction. Clinical Trial Registrations: NCT04559815 (Canada), NCT04537637 (Denmark), NCT05230615 (Italy), NCT04601740 (the Netherlands), NCT04601753 (Sweden), NCT04537624 (Switzerland), NCT04862923 (UK).