PIONEER 6 trial demonstrated non-inferiority of major adverse cardiovascular events (MACE) with oral semaglutide compared with placebo

Novo Nordisk announced that the PIONEER 6 trial achieved its primary endpoint by demonstrating non-inferiority of major adverse cardiovascular events (MACE) with oral semaglutide compared with placebo , both in addition to standard of care. The primary endpoint was defined as the MACE composite outcome of the first occurrence of cardiovascular death, non-fatal myocardial infarction or non-fatal stroke and non-inferiority for cardiovascular safety of oral semaglutide versus placebo was confirmed with a hazard ratio (HR) of 0.79 (p<0.001) in favour of oral semaglutide compared with placebo.

The results are based on an accumulation of 137 first major adverse cardiovascular events and a median follow-up time of 16 months. The main results from PIONEER 6 were presented at the American Diabetes Association (ADA) 79th Scientific Sessions and simultaneously published in The New England Journal of Medicine (NEJM). Oral semaglutide is an investigational glucagon-like peptide-1 (GLP-1) analogue in a pill. The MACE results were driven by the individual components of cardiovascular death [15 (0.9%) events with oral semaglutide vs 30 (1.9%) events with placebo, HR 0.49, p=0.03] and non-fatal strokes [12 (0.8%) events with oral semaglutide vs 16 (1.0%) events with placebo, HR 0.74, non-significant]. The number of non-fatal myocardial infarctions with oral semaglutide was not significantly different than placebo [37 (2.3%) events with oral semaglutide vs 31 (1.9%) events with placebo, HR 1.18, non-significant]. Among the secondary endpoints, the number of all-cause deaths was significantly lower in people treated with oral semaglutide compared with placebo [23 (1.4%) events vs 45 (2.8%) events, HR 0.51, , p=0.008]. The safety profile of oral semaglutide was consistent with that of the GLP-1 receptor agonist class and similar to those seen with subcutaneous semaglutide.

About PIONEER 6 and the PIONEER clinical trial programme : PIONEER 6 was an event-driven, pre-approval cardiovascular outcomes trial for oral semaglutide. It was a randomized, double-blinded, placebo-controlled trial evaluating the cardiovascular safety of oral semaglutide vs placebo when added to standard of care in 3,183 people with type 2 diabetes at high risk of cardiovascular events. The PIONEER phase IIIa clinical development program for oral semaglutide was a global development programme that enrolled 9,543 people with type 2 diabetes across 10 clinical trials.

See- Husain M et al. "Oral Semaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes". NEJM 2019. 10.1056/NEJMoa1901118.