Phase IIIa trials of oral semaglutide show efficacy in type 2 diabetes

Findings have been presented from two phase IIIa clinical trials evaluating oral semaglutide 14 mg, from Novo Nordisk, vs Jardiance (empagliflozin 25 mg) in PIONEER 2 and oral semaglutide 14 mg vs Victoza (liraglutide 1.8 mg) in PIONEER 4 over 52 weeks in adults with type 2 diabetes. In PIONEER 2, oral semaglutide 14 mg demonstrated a superior A1C reduction of 1.3% compared to a 0.9% reduction with empagliflozin 25 mg for the primary endpoint at 26 weeks (p<0.0001) and a statistically significant reduction in A1C for the secondary endpoint at 52 weeks. Furthermore, for the secondary endpoint, the reduction in body weight with oral semaglutide was similar to empagliflozin with no statistical differences at both 26 and 52 weeks (3.8 kg for oral semaglutide at both 26 and 52 weeks, 3.7 kg and 3.6 kg for empagliflozin, respectively).

In PIONEER 4, for the primary endpoint at 26 weeks, oral semaglutide 14 mg demonstrated a non-inferior reduction in A1C vs Victoza (1.2% vs 1.1%, respectively) and a superior reduction vs placebo (1.2% vs 0.2%, respectively) in adults with type 2 diabetes inadequately controlled on metformin, with or without a sodium-glucose co-transporter-2 (SGLT-2) inhibitor. For the secondary endpoint at 52 weeks, oral semaglutide demonstrated statistically significant reductions in A1C vs both Victoza (1.2% vs 0.9%, respectively) and placebo (1.2% vs 0.2%, respectively). For the secondary endpoint of change in body weight, oral semaglutide demonstrated superior reductions compared to both Victoza and placebo at 26 weeks (4.4 kg for oral semaglutide, 3.1 kg for Victoza and 0.5 kg for placebo) and statistically significant reductions compared to both at 52 weeks (4.3 kg for oral semaglutide, 3.0 kg for Victoza and 1.0 kg for placebo).

In PIONEER 2, the most common adverse event for oral semaglutide was nausea, which diminished over time, affecting 20% of people treated with oral semaglutide. The nausea rate for empagliflozin was 2%. The proportion of people who discontinued treatment due to adverse events was 11% for those treated with oral semaglutide compared to 4% for those treated with empagliflozin. In PIONEER 4, the most common adverse event for oral semaglutide was nausea, which diminished over time, affecting 20% of people treated with oral semaglutide. For people treated with Victoza and placebo, 18% and 4%, respectively, experienced nausea. The proportion of people who discontinued treatment due to adverse events was 11% for those treated with oral semaglutide compared to 9% with Victoza and 4% with placebo. Data from both trials were presented at the American Diabetes Association (ADA) 79th Scientific Sessions.