The results of two Phase 3 clinical trials, OASIS and PIONEER PLUS, suggest that higher doses of oral semaglutide may provide additional treatment options for patients with prediabetes or diabetes and obesity. These trials were presented at the American Diabetes Association’s 83rd Scientific Sessions and published in The Lancet.
Dr. Filip K. Knop from the University of Copenhagen, Denmark, presented the highlights of the OASIS-1 trial, which focused on patients with overweight or obesity without diabetes. The trial showed that oral semaglutide at a dose of 50 mg could be an effective treatment option for obesity, particularly for patients who prefer oral administration.
Dr. Vanita R. Aroda from Brigham and Women’s Hospital and Harvard University presented the key findings of the PIONEER PLUS trial, which included patients with inadequately controlled type 2 diabetes. The trial demonstrated that higher doses of once-daily oral semaglutide (25 mg and 50 mg) were associated with superior glycemic control, weight loss, and improvements in cardiometabolic risk factors compared to the currently approved 14-mg dose.
According to Marion Pragnell, Ph.D., the vice president of research and science at the ADA, there is a need for multiple treatment options as different patients respond differently to individual drugs. The oral formulation of semaglutide requires higher doses than the subcutaneous injection due to bioavailability. However, advancements in small molecule research may lead to the development of oral drugs with similar efficacy at lower doses in the future.
The oral version of semaglutide, marketed as Rybelsus, was approved in the US for type 2 diabetes at doses of 7 mg or 14 mg per day in 2019 but has not been approved for use in obesity.
Dr. Knop mentioned that in his clinical practice, about 25% of patients with type 2 diabetes prefer daily oral semaglutide, while the rest prefer weekly injected semaglutide. Having an oral formulation available alongside the subcutaneous option will allow individuals who struggle to lose weight with diet and physical activity alone to choose the administration method that suits them best.
Participants in the OASIS and PIONEER PLUS trials were instructed to take the once-daily study drug tablet in the morning while fasting, with up to half a glass of water at least 30 minutes before consuming any food, beverage, or oral medication.
Dr. Sean Wharton, the assigned discussant and final speaker at the ADA session, commented that OASIS-1 and PIONEER PLUS introduce an oral medication that is relatively easy to administer, scalable, and effective, with similar efficacy to injectable semaglutide, achieving a 15% weight loss at 52 weeks.