Abstract 15: Glycemic and body weight responses to oral semaglutide in the PIONEER trial program

Case: The PIONEER phase 3 program investigated glycemic response and other efficacy endpoints in patients (pts) with type 2 diabetes randomized to the glucagon-like peptide-1 analog oral semaglutide (sema; 3, 7 or 14 mg once daily), placebo (pbo) or an active comparator (empagliflozin [empa] 25 mg, sitagliptin [sita] 100 mg or liraglutide [lira] 1.8 mg once daily). This post-hoc analysis of the PIONEER 1-5 and 8 trials evaluated the response of any reduction in HbA (%) and/or body weight (%), and a clinically relevant composite endpoint of HbA1c reduction ≥1% and body weight loss ≥5%, with oral sema 14 mg vs. comparators at the end of treatment (26-78 weeks). Across trials, any reduction in HbA1c was observed in higher proportions of pts with oral sema (89- 95%) than with pbo (51-64%) or active comparators (82-88%). A simultaneous reduction in both HbA1c and body weight was seen in 72-86% of pts treated with oral sema. The composite of HbA1c reduction ≥1% and body weight loss ≥5% was achieved by 27-41% of pts with oral sema, 1-8% of pts with pbo, 11% with sita 100 mg, 18% with lira 1.8 mg, and 20% with empa 25 mg. Within each trial, the odds of achieving HbA1c reduction of ≥1% and body weight loss of ≥5% with oral sema 14 mg were significantly greater vs. all comparators.