Oral semaglutide showed superior reductions in blood sugar vs Jardiance(R) and non-inferior blood sugar reductions vs Victoza(R) in adults with type 2 diabetes at 26 weeks

PR79114

SAN FRANCISCO, June 9, 2019 /PRNewswire=KYODO JBN/ --

Abstracts 54-OR and 55-OR

Secondary data at 52 weeks demonstrated statistically significant blood sugar

reductions and statistically significant reduction of body weight vs both

Jardiance(R) and Victoza(R)

Findings presented today from two phase 3a clinical trials evaluated oral

semaglutide 14 mg vs Jardiance(R) (empagliflozin 25 mg) in PIONEER 2 and oral

semaglutide 14 mg versus Victoza(R) (liraglutide 1.8 mg) in PIONEER 4 over 52

weeks in adults with type 2 diabetes. Data from both trials were presented at

the American Diabetes Association (ADA) 79th Scientific Sessions. Oral

semaglutide is an investigational once-daily glucagon-like peptide-1 (GLP-1)

analogue in a pill.

In PIONEER 2, oral semaglutide 14 mg demonstrated a superior HbA1c 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

HbA1c 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 HbA1c vs Victoza(R) (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 HbA1c vs both Victoza(R) (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(R) and placebo at 26 weeks (4.4 kg for oral semaglutide, 3.1 kg for

Victoza(R) 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(R) 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(R) 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(R) and 4% with placebo.

These results are based on the primary statistical approach known as the

treatment policy (TPol) estimand, which was used to assess the effects of oral

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

medication.

"Despite their proven safety and efficacy, GLP-1 receptor agonists are

underutilised in clinical care" said Ildiko Lingvay, PIONEER 2 and 4

investigator and professor at the Departments of Internal Medicine and Clinical

Sciences, University of Texas Southwestern Medical Center, Dallas, Texas. "As a

treating physician, I'm encouraged by these findings and the potential of

investigational oral semaglutide to be the first oral GLP-1 receptor agonist

available as a new treatment option for people living with type 2 diabetes."

The following results from PIONEER 2 and 4 were also presented today at the ADA

and are based on the secondary statistical approach. The secondary statistical

approach is known as the trial product estimand and is used to assess the

effect of oral semaglutide, assuming all patients remained on trial product and

did not use rescue medication:

PIONEER 2:

- Oral semaglutide demonstrated statistically significant reductions in HbA1c

vs empagliflozin at 26 weeks (1.4% vs 0.9%, respectively) and at 52 weeks (1.3%

vs 0.8%, respectively).

- Oral semaglutide demonstrated a body weight reduction of 4.2 kg vs 3.8 kg

with empagliflozin at 26 weeks and a statistically significant reduction of 4.7

kg vs 3.8 kg at 52 weeks.

PIONEER 4:

- Oral semaglutide demonstrated statistically significant reductions in HbA1c

vs Victoza(R) and vs placebo at both 26 and 52 weeks (1.3% for oral

semaglutide, 1.1% for Victoza(R) and 0.1% for placebo at 26 weeks; 1.2% for

oral semaglutide, 0.9% for Victoza(R) and a 0.2% increase for placebo at 52

weeks).

- Oral semaglutide demonstrated statistically significant reductions in body

weight vs Victoza(R) and vs placebo at both 26 and 52 weeks (4.7 kg for oral

semaglutide, 3.2 kg for Victoza(R) and 0.7 kg for placebo at 26 weeks; 5.0 kg

for oral semaglutide, 3.1 kg for Victoza(R) and 1.2 kg for placebo at 52

weeks).

About PIONEER 2, PIONEER 4 and the PIONEER clinical trial programme

PIONEER 2 was a 52-week, randomised, open-label, active-controlled,

parallel-group, multicentre, multinational trial with two arms comparing the

efficacy and safety of oral semaglutide 14 mg with empagliflozin 25 mg in

people with type 2 diabetes, inadequately controlled on metformin. 822 people

were enrolled in PIONEER 2 and randomised 1:1 to receive either oral

semaglutide or empagliflozin once daily. The primary endpoint was change in

HbA1c from baseline to week 26 and the confirmatory secondary endpoint was

change in body weight from baseline to week 26. Additional key secondary

endpoints included change in HbA1c and body weight from baseline to week 52.

PIONEER 4 was a 52-week, randomised, double-blinded, double-dummy, active- and

placebo-controlled, parallel-group, multicentre, multinational trial with three

arms comparing the efficacy and safety of oral semaglutide 14 mg compared to

Victoza(R) (1.8 mg liraglutide) or placebo in people with type 2 diabetes,

inadequately controlled on metformin with or without an SGLT-2 inhibitor.

PIONEER 4 randomised 711 people in a 2:2:1 manner to receive either oral

semaglutide, Victoza(R) or placebo once-daily. The primary endpoint was change

from baseline to week 26 in HbA1c. Key secondary endpoints included change in

HbA1c and body weight from baseline to week 52.

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

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

across 10 clinical trials.

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[http://www.facebook.com/novonordisk],

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References

1. Montanya E, Rosenstock J, Canani LH, et al. Oral semaglutide vs

empagliflozin added-on to metformin monotherapy in uncontrolled type 2

diabetes: PIONEER 2. Abstract number 54-OR, American Diabetes Association 79th

Scientific Session, San Francisco, US; 7-11 June 2019

2. Pratley RE, Amod A, Hoff ST, et al. Oral Semaglutide vs Liraglutide and

Placebo in T2D: PIONEER 4. Abstract number 55-OR, American Diabetes Association

79th Scientific Session, San Francisco, US; 7-11 June 2019

Further information

Media:

Katrine Sperling, +45 4442 6718, krsp@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