Novo Nordisk has announced the headline results from PIONEER 3, a phase
IIIa trial with oral semaglutide for the treatment of adults with type 2
diabetes. Oral semaglutide is an investigational GLP-1 analogue taken
once daily as a tablet. The 78-week trial investigated the efficacy and
long-term safety of 3, 7 and 14 mg oral semaglutide compared with 100 mg
sitagliptin in 1,864 people with type 2 diabetes inadequately
controlled with metformin, with or without sulfonylurea. The
confirmatory endpoints were assessed after 26 weeks of treatment.GHRP-2 powder,GHRP 2 powder
Two distinct statistical approaches to evaluating the effects of oral
semaglutide were applied in the PIONEER 3 trial; a primary statistical
approach required by recent regulatory guidance evaluating the effect
regardless of discontinuation of treatment and use of rescue medication,
and a secondary statistical approach describing the effect while on
treatment and without use of rescue medication. The trial achieved its
primary objective according to the primary statistical approach by
demonstrating statistically significant and superior reductions in HbA1c
with oral semaglutide 7 and 14 mg compared to sitagliptin at week 26.
Furthermore, people treated with oral semaglutide 7 and 14 mg achieved
statistically significant and superior reductions in body weight
compared to sitagliptin at week 26.When applying the secondary
statistical approach for week 26 and week 78, respectively, people
treated with 7 and 14 mg oral semaglutide experienced statistically
significantly greater reductions in HbA1c of 1.1% and 0.7% with 7 mg
oral semaglutide, 1.4% and 1.1% with 14 mg oral semaglutide compared to
0.8% and 0.4% with sitagliptin. Reductions in HbA1c with 3 mg oral
semaglutide at 26 and 78 weeks were 0.5% and 0.3%, respectively, and the
reduction was statistically significantly less than sitagliptin at 26
week, but was not statistically different at week 78. Reductions in body
weight from baseline were statistically significantly greater with 3, 7
and 14 mg oral semaglutide at week 26 and 78, respectively, with
reductions of 1.2 and 1.9 kg for 3 mg oral semaglutide, 2.2 and 2.7 kg
for 7 mg oral semaglutide and 3.3 and 3.5 kg for 14 mg oral semaglutide
compared to 0.7 and 1.1 kg with sitagliptin.
In this 78-week trial, oral semaglutide was well-tolerated and with a
profile consistent with GLP-1-based therapy. The most common adverse
event for oral semaglutide was mild to moderate nausea, which diminished
over time. In PIONEER 3, 7-15% of people treated with oral semaglutide
experienced nausea, compared to 7% of people treated with sitagliptin.
The proportion of people who discontinued treatment due to adverse
events was 6-12% for people treated with oral semaglutide compared to 5%
with sitagliptin.
The PIONEER phase IIIa clinical development programme for oral
semaglutide is a global development programme with enrolment of 8,845
people with type 2 diabetes across 10 clinical trials, which are all
expected to complete in 2018.
