Time Spent in Glycemic Control After Initiating Treatment With Oral Semaglutide Versus Empagliflozin: An Exploratory Analysis of the PIONEER 2 Trial

An objective in the management of type 2 diabetes (T2D) is to achieve and maintain HbA1c targets, but the duration of time spent in glycemic control is unknown for oral semaglutide. In this exploratory analysis, the duration of time in glycemic control (HbA1c <7.0% and <6.5%) during the PIONEER 2 trial (NCT02863328) was assessed. Patients with uncontrolled T2D (N=822; HbA1c 7.0-10.5%) were randomized to oral semaglutide 14 mg or empagliflozin 25 mg, both once daily. Both drugs underwent dose escalation over 8 weeks. For this analysis, outcomes were evaluated using the on-treatment without rescue medication observation period. Baseline characteristics were similar between treatment arms. Mean baseline HbA1c for both arms was 8.1%. More patients receiving semaglutide vs empagliflozin achieved HbA1c <7.0% (78% vs 60%), and HbA1c remained <7% for the following lengths of time: ≥14 weeks (65% vs 48%); ≥26 weeks (56% vs 38%); and ≥38 weeks (46% vs 28%). During treatment, the mean duration of time spent at HbA1c <7.0% and <6.5% was 27 weeks and 16 weeks for semaglutide, and 19 weeks and 7 weeks for empagliflozin. Based on the trial product estimand, the odds of patients achieving HbA1c <7.0% at both week 26 and 52 were significantly greater with semaglutide vs empagliflozin (estimated OR 4.12 [95% CI 2.94, 5.76]; p<0.0001). Despite an 8-week dose escalation schedule, nearly half of patients receiving semaglutide had HbA1c <7.0% for ≥70% of the 52-week treatment duration. These data suggest that patients spend more time in glycemic control during treatment with semaglutide vs empagliflozin.