2843-LB: HbA1c and Weight Outcomes for Individuals with T2D Persistent on 25mg Oral Semaglutide: A PIONEER PLUS Post-Hoc Analysis

Introduction and Objective: The PIONEER PLUS trial was designed to test the efficacy of higher investigational doses of once daily oral semaglutide (OS), 25 and 50mg, in a population of T2D individuals inadequately controlled on 1-3 oral antidiabetic drugs (OADs). The trial demonstrated improvements in HbA1c and body weight (BW) for the 25mg dose (-1.8% HbA1c, -6.7kg) compared to the approved 14mg dose (-1.5 HbA1c, -4.4kg). Clinicaltrials.gov as NCT04707469. Methods: This post-hoc analysis of the PIONEER PLUS trial (n=1071) assessed those individuals who were titrated to the approved OS 14mg dose or the experimental 25mg dose and maintained that dose through the end of the trial. This post-hoc analysis is different from the originally published trial product estimand as it excludes individuals who either discontinued therapy or stepped down a dose throughout the trial period. Outcomes assessed are changes from baseline to 52 weeks in both HbA1c and body weight. Results: At the end of the 52-week trial period there were 606 individuals who had maintained either the 14mg (n=334) or 25mg (n=272) dose. Those persistent on the 25mg dose had a higher percentage of females compared to those persistent on 14mg (39.3%, 35.3%) but were overall similar in race/ethnicity, region, diabetes duration, BMI and smoking status. Individuals persistent on 25mg OS experienced a greater HbA1c reduction of -2.1% (baseline HbA1c 9.0%) compared to -1.6% (baseline HbA1c 8.9%) for those on 14mg. Additionally, those persistent on the 25mg dose experienced a greater BW reduction -7.6kg (7.70%, baseline 98.6kg) compared to -4.40kg (4.45%, baseline 98.8kg) at the end of 52 weeks (each p0.0001). Conclusion: In this post-hoc analysis of PIONEER PLUS individuals persistent on 25mg OS experienced greater reductions in HbA1c and BW compared to those persistent on 14mg. These results indicate greater glycemic and BW benefits in individuals with T2D persistent to treatment relative to the original trial product and treatment policy estimands. Disclosure Y. Patel: Other - Pre-Doctoral Fellowship; Current; Novo Nordisk. J. Noone: Employee; Current; Novo Nordisk. C.K. R: None. C. Muhammad: Employee; Current; Novo Nordisk. Stock/Shareholder; Current; Novo Nordisk.