Oral Semaglutide 7 mg and 14 mg Doses Showed Superior Reductions in Blood Sugar and Weight Compared to Sitagliptin at 26 Weeks in Data Presented at ENDO

PR77988

NEW ORLEANS, LA., Mar. 24, 2019, /PRNewswire=KYODO JBN/--

Oral semaglutide 7 mg and 14 mg demonstrated superior HbA1c and body weight

reductions compared to Januvia(R) (sitagliptin 100 mg). Non-inferiority for

oral semaglutide 3 mg for HbA1c reductions at 26 weeks was not confirmed.

Presented today at the Endocrine Society Annual Meeting in New Orleans,

Louisiana, with simultaneous publication in the Journal of the American Medical

Association (JAMA)1, PIONEER 3 was a phase 3a 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.

"Many people living with type 2 diabetes do not meet their blood glucose

targets despite many available oral antidiabetic therapies," said Dr Dale

Allison, PIONEER 3 investigator and director of medical research at the

Hillcrest Family Health Center, Waco, Texas. "The PIONEER 3 findings are

encouraging, as oral semaglutide demonstrated a clinically significant

improvement in HbA1c and this investigational therapy has the potential to

become the first oral GLP-1 receptor agonist for those living with type 2

diabetes."

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 approacha, 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 approachb 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.

About PIONEER 3 and the PIONEER clinical trial programme

PIONEER 3 was a 78-week, randomised, double-blind, double-dummy,

active-controlled, parallel-group, multicentre, multinational trial with four

arms comparing the efficacy and safety of oral semaglutide 3 mg, 7 mg and 14 mg

with sitagliptin 100 mg in people with type 2 diabetes inadequately controlled

with metformin, with or without sulfonylurea. PIONEER 3 randomised 1,864 people

in a 1:1:1:1 manner to receive either a dose of oral semaglutide 3 mg, 7 mg and

14 mg or sitagliptin 100 mg once daily. The primary endpoint was change in

HbA1c, and the confirmatory secondary endpoint was change in body weight, both

from baseline to week 26.

The PIONEER phase 3a clinical development programme for oral semaglutide was a

global development programme that enrolled 9,543 people with type 2 diabetes

across 10 clinical trials. The programme was completed in 2018.

Novo Nordisk is a global healthcare company with more than 95 years of

innovation and leadership in diabetes care. This heritage has given us

experience and capabilities that also enable us to help people defeat obesity,

haemophilia, growth disorders and other serious chronic diseases. Headquartered

in Denmark, Novo Nordisk employs approximately 43,200 people in 80 countries

and markets its products in more than 170 countries. For more information,

visit novonordisk.com, Facebook, Twitter, LinkedIn, YouTube.

a In PIONEER 3, two distinct statistical approaches were used to evaluate the

effects of oral semaglutide. The primary statistical approach is known as the

treatment policy (TPol) estimand and it was used to assess the effects of oral

semaglutide regardless of discontinuation of trial product and/or use of rescue

medication.

b The secondary statistical approach is known as the trial product estimand and

it was used to assess the effect of oral semaglutide, assuming all patients

remained on trial product and did not use rescue medication.

References

1. Rosenstock J, et al. Effect of Additional Oral Semaglutide vs Sitagliptin on

Glycated Hemoglobin in Adults with Type 2 Diabetes Uncontrolled with Metformin

alone or with Sulfonylurea: the PIONEER 3 Randomized Clinical Trial. JAMA.

2019;321(15):1–15. doi:10.1001/jama.2019.2942

Further information  

Media:    

Mette Kruse Danielsen

+45-4442-3883

mkd@novonordisk.com

Michael Bachner (US)

+1-609-664-7308

mzyb@novonordisk.com

Investors:    

Peter Hugreffe Ankersen

+45-3075-9085

phak@novonordisk.com

Valdemar Borum Svarrer

+45-3079-0301

jvls@novonordisk.com

Ann Sondermolle Rendbaek

+45-3075-2253

arnd@novonordisk.com

Kristoffer Due Berg (US)

+1-609-235 2989

krdb@novonordisk.com

SOURCE: Novo Nordisk