Once Daily Oral Semaglutide 50 mg Improves Physical Functioning in the OASIS 1 Trial

Background: In OASIS 1, the estimated mean percentage body weight change from baseline to week 68 was -15.1% with once-daily oral semaglutide 50 mg and -2.4% with placebo; comparable to weight loss with once-weekly subcutaneous semaglutide 2.4 mg. In this analysis, the impact of semaglutide vs placebo on physical functioning (PF) was evaluated based on patient-reported data from the Impact of Weight on Quality of Life-Lite Clinical Trials Version (IWQOL-Lite-CT) and Short Form-36v2 Health Survey acute version (SF-36v2) instruments. Methods: In the OASIS 1 trial (NCT05035095), 667 adults with overweight or obesity were randomized 1:1 to semaglutide or placebo, plus lifestyle intervention. Changes from baseline to week 68 in the PF domains of the IWQOL-Lite-CT and SF-36v2 were assessed by analysis of covariance for the treatment policy estimand for all participants and for a subgroup with poor baseline PF (n = 88; 13.2%) (defined as participants who responded "Poor" on PF of the Patient Global Impression of Severity questionnaire). The number of participants achieving a meaningful within-person improvement in PF in IWQOL-Lite-CT (≥14.6 points), and SF-36v2 (≥3.7 points) were also assessed. Anchor-based methods were used to derive these cut-off scores. Results: Significantly greater improvements from baseline to week 68 with semaglutide versus placebo in the IWQOL-Lite-CT PF score were observed for all participants (estimated treatment difference [ETD] 10.5 points, 95% confidence interval [CI] 7.5, 13.6) and for ticipants with baseline PF (ETD 14.4 points, 95% Cl 4.4, 24.4). Similar results were observed in the SF-36v2 PF score (all participants, ETD 2.3 points, 95% CI 1.4, 3.2; participants with poor baseline PF, ETD 4.2 points, 95% CI 0.9, 7.5). Semaglutide-treated participants were more likely to achieve meaningful improvement in PF at week 68 vs placebo in the IWQOL-Lite-CT (50% vs 31%, odds ratio [OR] 2.8, 95% CI 1.9, 4.1) and in the SF-36v2 (37% vs 20%, OR 2.9, 95% CI 1.9, 4.5). Greater categorical weight loss was associated with greater improvements in PF in both instruments (data not shown). Conclusions: Once-daily oral semaglutide 50 mg provided meaningful improvement in physical functioning in participants with overweight/ obesity, including those with poor physical functioning at baseline.