The results of the phase 3a trials PIONEER 4 and PIONEER 7 show statistically significant and superior reductions in HbA1c and weight with semaglutide compared to liraglutide and sitagliptin, respectively, in patients with type 2 diabetes (T2DM).

The PIONEER 4 was a 52-week, randomized, double-blinded, double-dummy, active- and placebo-controlled, parallel-group, multicenter, multinational trial with three arms, evaluating the efficacy and safety of 14 mg semaglutide compared with 1.8 mg liraglutide and placebo in 711 T2DM patients inadequately controlled by metformin and with or without an SGLT2-inhibitor. At week 26 and 52, T2DM patients with semaglutide had a significant reduction of HbA1c of 1.3% and 1.2% compared to 1.1% and 0.9% with liraglutide and placebo showed a reduction of 0.1% and an increase of 0.2%. Significant reductions in body weight from baseline 4.7 and 5.0 kg at 26 and 52 weeks were observed with semaglutide, compared to 3.2 and 3.1 kg with liraglutide and 0.7 and 1.2 kg with placebo.

Semaglutide was well-tolerated and the most common side effect was mild to moderate nausea (20% of patients treated with semaglutide, 18% of patients with liraglutide and 4% of patients with placebo), which disappeared over time.

The PIONEER 7 was a 52- week, randomized, open-label, active-controlled, parallel-group, multicenter, multinational trial with two arms, evaluating the efficacy and safety of semaglutide using a flexible dose adjustment (3, 7, or 14 mg) based on clinical evaluation compared to 100 mg sitagliptin in 504 T2DM patients, inadequately controlled on 1-2 antidiabetic drugs. A significant reduction in HbA1c of 1.4% with semaglutide compared to 0.7% with sitagliptin at week 52 was observed. The target HbA1c below 7% after 52 weeks was achieved by 63% of patients treated with semaglutide compared to 28% of patients with sitagliptin, a statically significant difference. Body weight reductions were also significantly greater at week 52 with semaglutide (2.9 kg) compared to sitagliptin (0.8 kg).

Semaglutide was well-tolerated and the most common adverse event was mild to moderate nausea (21% of patients treated with semaglutide, 2% of patients with sitagliptin), which disappeared over time.

The PIONEER phase 3a clinical development program for oral semaglutide is a global development program with enrollment of 8,845 people with T2DM across 10 clinical trials, which are all expected to complete in 2018.

Source: press release Novo Nordisk, June 20, 2018