Real-World Use of Oral Semaglutide in Adults with Type 2 Diabetes in the PIONEER REAL Netherlands Multicentre, Prospective, Observational Study

Abstract

Introduction: In this phase 4, multicentre, prospective, non-interventional PIONEER REAL Netherlands study, we assessed clinical outcomes associated with once-daily oral semaglutide use in real-world clinical practice in adults living with type 2 diabetes (T2D) naïve to injectable glucose-lowering medication.

Methods: Participants initiated on oral semaglutide were followed for 34-44 weeks. Change in glycated haemoglobin (HbA1c) from baseline (BL) to end of study (EOS) was the primary endpoint; secondary endpoints included change in body weight (BW) from BL to EOS, the proportion of participants with HbA1c < 7.0% at EOS and the composite endpoints of HbA1c reduction ≥ 1.0%-points with BW reduction ≥ 3% or ≥ 5% at EOS. Treatment satisfaction was assessed using the Diabetes Treatment Satisfaction Questionnaire (DTSQ status/change). Safety was evaluated in all participants who initiated oral semaglutide treatment.

Results: Oral semaglutide was initiated in 187 participants; 94.1% completed the study and 78.6% remained on treatment at EOS. At BL, 54.0% of participants were male, mean age was 58.8 years, mean duration of T2D was 8.7 years and mean body mass index was 35.1 kg/m²; mean HbA1c was 8.6% and mean BW was 103.1 kg. Significant improvements from BL to EOS were observed for HbA1c and BW (estimated change [95% confidence interval]: - 1.16%-points [- 1.48 to - 0.85]; p < 0.0001, and - 5.84 kg [- 6.88 to - 4.80]; p < 0.0001, respectively). At EOS, 47.5% of participants had an HbA1c level < 7.0%; 41.8% and 35.5% of participants achieved composite endpoints of HbA1c reduction ≥ 1.0%-points plus BW reduction ≥ 3% or ≥ 5%, respectively. DTSQ status and change scores improved by 2.1 (p = 0.0003) and 10.8 points (p < 0.0001), respectively. Oral semaglutide was easy or very easy to consume for 81.5% of participants. Adverse events were mostly mild/moderate, with gastrointestinal disorders being the most common.

Conclusion: In this real-world population, we reported clinically significant reductions in HbA1c and BW, improved treatment satisfaction and no new safety concerns. A graphical abstract is available with this article.

Clinical trial registration: NCT04601740.

Keywords: Body weight; GLP-1 receptor agonist; Glycaemic control; HbA1c; Incretin therapy; Real-world evidence; Semaglutide; Type 2 diabetes.

Fig. 1

Estimated change in HbA1c from baseline to EOS (N = 168). Data are from the in-study observation period. At week 0, observed mean HbA1c at baseline for participants with at least one post-baseline assessment is plotted. Estimated HbA1c change is analysed using an adjusted model, with baseline HbA1c, age, baseline BMI, time and time-squared as covariates, and sex, glucose-lowering agents at baseline, diabetes duration and site as fixed factors with random intercept and time (slope). The outer lines of the band represent 95% CI. BMI body mass index, CI confidence interval, EOS end of study, HbA1c glycated haemoglobin

Fig. 2

Estimated change in body weight from baseline to EOS (N = 165). Data are from the in-study observation period. At week 0, observed mean body weight at baseline for participants with at least one post-baseline assessment is plotted. Body weight change is analysed using an adjusted model, with baseline body weight, age, baseline BMI, time and time-squared as covariates, and sex, glucose-lowering agents at baseline, diabetes duration and site as fixed factors with random intercept and time (slope). The outer lines of the band represent 95% CI. BMI body mass index, CI confidence interval, EOS end of study

Fig. 3

Proportion of participants a achieving HbA1c targets and b with composite endpoints of HbA1c and body weight reductions at EOS. a n = 160, b n = 141. EOS end of study, HbA1c glycated haemoglobin

Fig. 4

Participant-reported satisfaction: a absolute treatment satisfaction measured with DTSQs and b relative treatment satisfaction measured with DTSQc. Data are for the in-study observation period. For DTSQs, 0 = very dissatisfied and 36 = very satisfied. For DTSQc, − 18 = much less satisfied and + 18 = much more satisfied. CI confidence interval, DTSQc Diabetes Treatment Satisfaction Questionnaire change, DTSQs Diabetes Treatment Satisfaction Questionnaire status, EOS end of study, SD standard deviation. ^aObserved change was 10.78 (SD 6.15)