Oral semaglutide shows statistically significantly greater reductions in HbA1c and weight compared to Victoza® and sitagliptin in the PIONEER 4 and 7 trials

Bagsværd, Denmark, 20 June 2018 - Novo Nordisk today announced the successful completion and headline results of the phase 3a trials PIONEER 4 comparing oral semaglutide as a treatment for adults with type 2 diabetes to Victoza^® (1.8 mg liraglutide) and placebo, and PIONEER 7 comparing oral semaglutide as a treatment for adults with type 2 diabetes to sitagliptin 100 mg. Oral semaglutide is a new GLP-1 analogue taken once daily as a tablet.

Two distinct statistical approaches to evaluate the effects of oral semaglutide were applied in the PIONEER 4 and 7 trials; a primary statistical approach^[1] required by recent regulatory guidance, evaluating the effect regardless of discontinuation of treatment and use of rescue medication, and a secondary statistical approach^[2] describing the effect while on treatment and without use of rescue medication.

PIONEER 4
PIONEER 4 was a 52-week double-blinded, double-dummy trial investigating the efficacy and safety of 14 mg oral semaglutide compared with Victoza^® 1.8 mg and placebo in 711 people with type 2 diabetes inadequately controlled on metformin, with or without an SGLT-2 inhibitor.

PIONEER 4 achieved its primary objective according to the primary statistical approach by demonstrating a non-inferior reduction in HbA_1c and statistically significant and superior weight loss at 26 weeks with oral semaglutide compared to Victoza^®. Furthermore, oral semaglutide provided statistically significant and superior reductions in HbA_1c and weight compared to placebo.

When applying the secondary statistical approach for week 26 and week 52, respectively, people treated with oral semaglutide experienced a reduction in HbA_1c of 1.3% and 1.2% compared to 1.1% and 0.9% with Victoza^® whereas placebo declined by 0.1% and increased by 0.2%. Reductions in HbA_1c were statistically significantly greater with oral semaglutide compared to both Victoza^® and placebo. Reduction in body weight from baseline was statistically significantly greater with oral semaglutide at 4.7 and 5.0 kg at 26 and 52 weeks, respectively, compared to 3.2 and 3.1 kg with Victoza^®, and 0.7 and 1.2 kg with placebo. The American Diabetes Association (ADA) treatment target of HbA_1c below 7.0% was achieved by 69% of people treated with oral semaglutide, 63% of people treated with Victoza^® and 18% of people treated with placebo after 52 weeks; the difference between oral semaglutide and placebo was statistical significant.