Oral semaglutide compared to Januvia in patients with type 2 diabetes

Oral semaglutide 7 mg and 14 mg demonstrated superior HbA1c and body weight reductions compared to Januvia (sitagliptin 100 mg) . Non-inferiority for oral semaglutide 3 mg for HbA1c reductions at 26 weeks was not confirmed. Presented at the Endocrine Society Annual Meeting in New Orleans, Louisiana, with simultaneous publication in the Journal of the American Medical Association (JAMA).

PIONEER 3 was a phase IIIa trial investigating the efficacy and long-term safety of oral semaglutide 3 mg, 7 mg and 14 mg compared with sitagliptin 100 mg in adults with type 2 diabetes inadequately controlled with metformin, with or without sulfonylurea, over 78 weeks. Oral semaglutide is an investigational once-daily glucagon-like peptide-1 (GLP-1) analogue in a pill.

In PIONEER 3 , the primary endpoints of HbA1c and confirmatory secondary endpoint of change in body weight were assessed after 26 weeks of treatment. When applying the primary statistical approach, oral semaglutide 7 mg and 14 mg demonstrated superior HbA1c reductions of 1.0% and 1.3% at 26 weeks, compared to a 0.8% reduction with sitagliptin (both p<0.001). Oral semaglutide 3 mg demonstrated a reduction in HbA1c of 0.6%; non-inferiority compared to sitagliptin was not confirmed (p=0.09). Furthermore, at 26 weeks, oral semaglutide 7 mg and 14 mg demonstrated superior body weight reductions of 2.2 kg and 3.1 kg, both compared to a 0.6 kg reduction for sitagliptin (p<0.01). When applying the secondary statistical approach at week 26, oral semaglutide 7 mg and 14 mg demonstrated statistically significant reductions in HbA1c of 1.1% and 1.4%, respectively, compared to a 0.8% reduction with sitagliptin (both p<0.001). Reductions in HbA1c seen with oral semaglutide 3 mg were 0.5% and compared to the reductions seen with sitagliptin, the difference is statistically significant in favour of sitagliptin. Reductions in body weight from baseline were statistically significant in favour of all three oral semaglutide doses. In a supportive secondary endpoint at week 78, oral semaglutide 14 mg demonstrated statistically significant reductions in HbA1c compared to sitagliptin for both statistical approaches (1.1% vs 0.7%; p <0.001a; 1.1% vs 0.4%; p<0.001b). There was no statistically significant difference with oral semaglutide 3 mg (both estimands) or 7 mg (TPol estimand) vs sitagliptin. Reductions in body weight from baseline, which was dose dependent, were statistically significant with oral semaglutide 3 mg, 7 mg and 14 mg at week 78 with reductions of 1.8 kg, 2.7 kg and 3.2 kg, respectively, compared to a 1.0 kg reduction with sitagliptin (all p<0.05a) and 1.9 kg, 2.7 kg and 3.5 kg, respectively, compared to a 1.1 kg reduction with sitagliptin (all p<0.05b).

In this 78-week trial, the most common adverse event for oral semaglutide was nausea, which was dose dependent, affecting 7.3% to 15.1%. The nausea rate for sitagliptin was 6.9%. People taking oral semaglutide 3 mg, 7 mg and 14 mg reported serious adverse events at a rate of 13.7%, 10.1% and 9.5%, respectively, compared to a rate of 12.4% of those taking sitagliptin. The proportion of people who discontinued treatment due to adverse events was 5.6%, 5.8% and 11.6% for people treated with oral semaglutide 3 mg, 7 mg and 14 mg, respectively, compared to 5.2% with sitagliptin.