Oral treatment with the glucagon-like-peptide 1 (GLP-1) receptor agonist semaglutide once-daily reduced HbA1c and body weight compared with placebo or sitagliptin in T2DM patients in the PIONEER 1 and 3 phase 3a trials. The trials investigated the efficacy and safety of 3, 4 and 7 mg oral semaglutide in comparison with placebo or 100 mg DDP-4 inhibitor sitagliptin.

PIONEER 1 showed decreased HbA1c levels of 0.8%, 1.3% and 1.5% after treatment with respectively 3, 7 and 14 mg semaglutide at week 26, whereas placebo resulted in 0.1% reduction (P<0.001). In PIONEER 3 a significant HbA1c reduction of 1.1% and 0.7% was observed in respectively week 26 and 78 after oral administration of 7 mg semaglutide, and 14 mg resulted in 1.4% and 1.1% reduction, compared with 0.8% and 0.4% for sitagliptin.

Besides reduced HbA1c levels, a significant reduction in body weight of 4.1 kg was observed in PIONEER 1 after treatment with 14 mg semaglutide, in comparison with placebo (P<0.001). PIONEER 3 demonstrated a reduction of 2.2 and 2.7 kg in week 26 and 78, respectively with 7 mg semaglutide and 3.3 kg in week 26 and 3.5 kg in week 78 with 14 mg semaglutide, compared with respectively 0.7 kg and 1.1 kg for sitagliptin.

Oral semaglutide was well tolerated, with mild or moderate nausea as most common adverse effect (6-16% in PIONEER 1 and 7-15% in PIONEER 3). Treatment discontinuation due to adverse effects occurred in 2-7% of patients treated with semaglutide in PIONEER 1 and in 6-12% in PIONEER 3.

The semaglutide tablet consists of sodium N-(8-[2-hydroxybenzoyl] amino) caprylate which facilitates the absorption of semaglutide from the stomach, enabling oral dosing.

PIONEER 1 (26 weeks) was a randomized, double-blinded, placebo-controlled, four-armed, parallel-group, multicenter, multinational trial evaluating the efficacy and safety of three dose levels of once-daily semaglutide, compared with placebo in 703 T2DM patients.

PIONEER 3 (78 weeks) was a randomized, double-blind, double-dummy, active-controlled, parallel-group, multicenter, multinational trial also investigating the efficacy and safety of 3, 7 and 14 mg semaglutide in 1,864 T2DM patients inadequately controlled with metformin, with or without sulfonylurea, compared with 100 mg sitagliptin.

The primary outcome of both trials consisted of changes in HbA1c levels from baseline to week 26. Secondary outcomes were the percentage patients with HbA1c levels <7% and changes in body weight in PIONEER 1. PIONEER 3 measured changes in HbA1c levels and body weight from baseline to week 78.

The PIONEER phase 3a global development program for oral semaglutide includes 8,845 T2DM participants across ten clinical trials, which are all expected to be completed in 2018.

Source: press release Novo Nordisk, June 23, 2018Source: press release Novo Nordisk, June 28, 2018