FDA approved subcutaneous semaglutide (ozempic) in December 2017. Clinical trials and experience have shown that semaglutide helps with A1c lowering and weight loss. Additionally, SUSTAIN 6 trial proved its cardiovascular safety.
The current study PIONEER 6, published in the New England Journal of Medicine, addresses the cardiovascular safety of oral semaglutide in diabetes patients at “high risk” for adverse ASCVD events. Age greater than 50 with established cardiovascular disease or chronic kidney disease, or age greater than 60 with CVD risk factors defined the “high risk” status in study participants.
A group of 3200 adults was randomized to receive oral semaglutide or placebo. Patients’ mean age was 66 years. Investigators followed subjects for about 16 months. Final analysis revealed that participants receiving oral semaglutide experienced 20% less major adverse cardiovascular events (MACE) than placebo counterparts. Lower rates of CV death and death from any cause seem to be the main drivers of the reduced primary endpoint.
Although MACE occurred less frequently in the semaglutide group, the trial was designed to evaluate non-inferiority (safety) and not superiority (benefits). These findings are reassuring towards a positive FDA approval for the oral semaglutide. Such an endorsement would place the first oral GLP-1 agonist on the market.