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Explore PIONEER studies:

Diet and excercise

Oral semaglutide vs

placebo

Participants: 703
: 26 weeks

Add-on to OAD

Oral semaglutide vs

SGLT2i

Participants: 822
: 52 weeks

Oral semaglutide vs

DPP4i

Participants: 1864
: 78 weeks

Oral semaglutide vs

GLP-1 RA

 
Participants: 711
: 52 weeks

Oral semaglutide vs

DPP4i

(flexible dose adjustment)
Participants: 504
: 52 weeks

Insulin users

Oral semaglutide vs

placebo

(add-on to insulin)
Participants: 731
: 52 weeks

Special populations

Oral semaglutide + SOC vs

placebo + SOC

(CVOT)
Participants: 3183
: Event driven

Oral semaglutide vs

placebo

(renal impairment)
Participants: 324
: 26 weeks

Key results of PIONEER 12

26 week results

Results are based on treatment policy estimand which evaluates the treatment effect for all randomised patients regardless of trial product discontinuation and use of rescue medication.

PIONEER 1 summary

PIONEER 1 trial compared the efficacy and safety of oral semaglutide as monotherapy vs placebo in patients with type 2 diabetes managed by diet and exercise only. 

 

Oral semaglutide demonstrated superior and clinically relevant reductions in HbA1c (all doses) and body weight (14 mg dose) vs placebo. The proportion of patients achieving the HbA1c target of <7% was greater with oral semaglutide vs placebo.

Find the full publication at: 

Diabetes Care. 2019;42:1724–32

 

Comparator

Comparator:

Placebo

Population

Population:

Drug-naive adults with T2D

Paritcipants

Participants:

703

Duration

Duration :

26 weeks

Key results of PIONEER 23

52 week results

Results are based on treatment policy estimand which evaluates the treatment effect for all randomised patients regardless of trial product discontinuation and use of rescue medication.

PIONEER 2 summary

PIONEER 2 was an open-label trial which was the first to directly compare oral semaglutide with an SGLT2 inhibitor, empagliflozin, in patients with type 2 diabetes who were uncontrolled on metformin. 

 

Oral semaglutide was superior to empagliflozin in reducing HbA1c at 26 weeks. A significant reduction in HbA1c at week 52 was also observed for oral semaglutide compared to empagliflozin. More patients achieved the predefined HbA1c target of <7% with oral semaglutide than with empagliflozin at 26 and 52 weeks.

Find the full publication at: 

Diabetes Care. 2019;42:1724–32

Comparator

Comparator:

Empagliflozin 25 mg

Population

Population:

T2D patients on metformin only

Paritcipants

Participants:

822

Duration

Duration :

52 weeks

Key results of PIONEER 34

78-week results

Results are based on treatment policy estimand which evaluates the treatment effect for all randomised patients regardless of trial product discontinuation and use of rescue medication.

PIONEER 3 summary

PIONEER 3 compared the efficacy and assessed the long-term safety of oral semaglutide vs DPP4 inhibitor, sitagliptin, as add-on therapy to metformin with or without sulfonylurea in patients with type 2 diabetes. 

 

Oral semaglutide (14 mg) resulted in statistically significantly greater reductions in HbA1c and body weight at weeks 26 and 78, compared with sitagliptin 100 mg. Significantly greater proportions of patients achieved HbA1c levels lower than 7% with oral semaglutide vs sitagliptin.

Find the full publication at:
JAMA. 2019; 321:1466-1480

 

Comparator

Comparator:

Sitagliptin 100 mg

Population

Population:

T2D patients on metformin

Paritcipants

Participants:

1864

Duration

Duration :

78 weeks

Key results of PIONEER 45

52 week results

Results are based on treatment policy estimand which evaluates the treatment effect for all randomised patients regardless of trial product discontinuation and use of rescue medication.

PIONEER 4 summary

PIONEER 4 was the first trial to compare the efficacy and safety of oral semaglutide with a subcutaneously injected GLP-1RA, liraglutide, and placebo in patients with type 2 diabetes uncontrolled on metformin with or without an SGLT2i. 

 

Oral semaglutide 14 mg resulted in significantly greater reductions in HbA1c and body weight vs subcutaneous liraglutide 1.8 mg or placebo at 52 weeks. More patients on oral semaglutide achieved HbA1c target <7% than patients on liraglutide or placebo.

Find the full publication at:

Lancet. 2019;394:39-50

 

Comparator

Comparator:

Liraglutide 1.8 mg (daily subcutaneous) or placebo

Population

Population:

T2D patients on metformin

Paritcipants

Participants:

711

Duration

Duration :

52 weeks

Key results of PIONEER 76

52 week results

Results are based on treatment policy estimand which evaluates the treatment effect for all randomised patients regardless of trial product discontinuation and use of rescue medication.

PIONEER 7 summary

PIONEER 7 was an open-label trial where investigators used a flexible dosing approach to study the efficacy and safety of oral semaglutide versus the DPP4 inhibitor sitagliptin in people with type 2 diabetes, inadequately controlled on 1-2 oral antidiabetics. 

 

The trial demonstrated that the proportion of patients achieving an HbA1c target below 7% was statistically significantly greater with oral semaglutide compared to sitagliptin. The reductions in HbA1c and body weight were significantly greater with oral semaglutide compared to sitagliptin.

Find the full publication at: 

Lancet Diabetes Endocrinol. 2019;7:528-539

Comparator

Comparator:

Sitagliptin 100 mg

Population

Population:

T2D patients inadequately controlled on 1-2 oral antidiabetics

Paritcipants

Participants:

504

Duration

Duration :

52 weeks

Key results of PIONEER 87

52 week results

Results are based on treatment policy estimand which evaluates the treatment effect for all randomised patients regardless of trial product discontinuation and use of rescue medication.

PIONEER 8 summary

PIONEER 8 trial investigated the efficacy and safety of oral semaglutide versus placebo in patients with type 2 diabetes uncontrolled on insulin with or without metformin. 

 

Oral semaglutide (all doses) was superior to placebo in reducing HbA1c and body weight at week 26 and statistically significantly greater at week 52. The proportions of patients achieving HbA1c <7% was significantly greater with oral semaglutide vs placebo.

Find the full publication at: 

Diabetes Care. 2019;42:2262-2271

 

Comparator

Comparator:

Placebo

Population

Population:

T2D patients using insulin with or without metformin

Paritcipants

Participants:

731

Duration

Duration :

52 weeks

Key results of PIONEER 68

PIONEER 6 summary

PIONEER 6 trial assessed the cardiovascular outcomes of oral semaglutide in an event-driven trial involving patients at high CV risk. The study was designed as a non-inferiority pre-approval trial to exclude an unacceptable increase in CV risk compared with placebo. Patients received oral semaglutide 14 mg or placebo both in addition to standard of care. 

 

The primary outcome of first occurrence of 3-point MACE (composite of CV death, nonfatal myocardial infarction or nonfatal stroke) occurred in 3.8% of patients in the semaglutide group and 4.8% in the placebo group (hazard ratio 0.79; 95% CI: 0.57;1.11; p<0.001 for non-inferiority; p=0.17 for superiority). Thus, non-inferiority, but not superiority, was established for oral semaglutide vs placebo and CV safety for oral semaglutide confirmed in the PIONEER 6 trial.

Find the full publication at:
Diabetes Care. 2019;42:2262-2271

 

Comparator

Comparator:

Placebo

Population

Population:

T2D patients with high cardiovascular risk

:

3183

:

Event-driven

Key results of PIONEER 59

26 week results

Results are based on treatment policy estimand which evaluates the treatment effect for all randomised patients regardless of trial product discontinuation and use of rescue medication.

PIONEER 5 summary

PIONEER 5 investigated the efficacy and safety of oral semaglutide versus placebo in patients with type 2 diabetes and moderate renal impairment inadequately controlled on metformin, sulfonylurea alone or in combination with metformin, or basal insulin alone or in combination with metformin. 

 

Oral semaglutide was superior to placebo in decreasing HbA1c and body weight at week 26. More patients receiving oral semaglutide than placebo achieved the HbA1c target of <7%.

Find the full publication at:

Lancet Diabetes Endocrinol. 2019;7:515-527

 

Comparator

Comparator:

Placebo

Population

Population:

T2D patients with moderate renal impairment

Paritcipants

Participants:

326

Population

Population:

26 weeks

1.

RYBELSUS® [summary of product characteristics]. Bagsværd, Denmark: Novo Nordisk A/ S; April 2023.

2.

Aroda VR, Rosenstock J, Terauchi Y, et al. PIONEER 1: Randomized clinical trial of the efficacy and safety of oral semaglutide monotherapy in comparison with placebo in patients with type 2 diabetes. Diabetes Care. 2019; 42:1724-1732.

3.

Rodbard HW, Rosenstock J, Canani LH, et al. Oral semaglutide versus empagliflozin in patients with type 2 diabetes uncontrolled on metformin: The PIONEER 2 trial. Diabetes Care. 2019; 42:2272-2281.

4.

Rosenstock J, Allison D, Birkenfeld AL, 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; 321:1466-1480.

5.

Pratley R, Amod A, Hoff ST, et al. Oral semaglutide versus subcutaneous liraglutide and placebo in type 2 diabetes (PIONEER 4): a randomised, double-blind, Phase 3a trial. Lancet. 2019; 394:39-50.

6.

Pieber TR, Bode B, Mertens A, et al. Efficacy and safety of oral semaglutide with flexible dose adjustment versus sitagliptin in type 2 diabetes (PIONEER 7): a multicentre, open-label, randomised, Phase 3a trial. Lancet Diabetes Endocrinol. 2019;7:528-539.

7.

Zinman B, Aroda VR, Buse JB, et al. Efficacy, safety, and tolerability of oral semaglutide versus placebo added to insulin with or without metformin in patients with type 2 diabetes: The PIONEER 8 trial. Diabetes Care. 2019;42:2262-2271.

8.

Husain M, Birkenfeld AL, Donsmark M, et al. Oral semaglutide and cardiovascular outcomes in patients with type 2 diabetes. N Engl J Med. 2019;381:841-851.

9.

Mosenzon O, Blicher TM, Rosenlund S, et al. Efficacy and safety of oral semaglutide in patients with type 2 diabetes and moderate renal impairment (PIONEER 5): a placebo-controlled, randomized, Phase 3a trial. Lancet Diabetes Endocrinol. 2019;7:515-527.