The phase 3a double-blinded PIONEER 6 trial achieved its primary endpoint by demonstrating non-inferiority of major adverse cardiovascular events (MACE) with oral semaglutide, a glucagon-like peptide-1 receptor agonist (GLP-1RA), taken once daily 14 mg compared with placebo, both in addition to standard of care, in 3,183 adults with T2DM at high risk of CV events.
The results are based on the accumulated occurrence of 137 MACE, with a median follow-up time of 16 months. The primary endpoint of the PIONEER 6 trial was defined as the MACE composite outcome of the first occurrence of CV death, non-fatal MI or non-fatal stroke and showed an non-significant HR of 0.79 in favor of oral semaglutide compared with placebo.
The MACE results demonstrated by oral semaglutide were driven by a statistically significant reduction in CV death of 51% (HR: 0.49, P=0.03), while non-fatal MI (HR: 1.18, non-significant) or non-fatal stroke (HR: 0.74, non-significant) were broadly similarly distributed between the two treatment arms. In addition, a statistically significant reduction in all-cause mortality of 49% (HR: 0.51, P=0.008) in favor of oral semaglutide was observed.
The improvements in secondary endpoints including HbA1c, body weight and blood pressure were similar to results reported throughout the PIONEER program for oral semaglutide. Furthermore, the safety profile of oral semaglutide in PIONEER 6 was consistent with the established safety profile observed in previous PIONEER clinical trials.
PIONEER 6 was an event-driven, pre-approval CV outcomes trial for oral semaglutide. It was a randomized, double-blinded, placebo-controlled trial evaluating the CV safety of oral semaglutide vs placebo when added to standard of care in 3,183 people with T2DM at high risk of CV events.
The PIONEER phase 3a clinical development program for oral semaglutide is a global development program with enrolment of 8,845 people with T2DM across 10 clinical trials, which have all been completed in 2018.