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Explore PIONEER studies:
Diet and excercise
Oral semaglutide vs
placebo
Add-on to OAD
Oral semaglutide vs
SGLT2i
Oral semaglutide vs
DPP4i
Oral semaglutide vs
GLP-1 RA
Oral semaglutide vs
DPP4i
Insulin users
Oral semaglutide vs
placebo
Special populations
Oral semaglutide + SOV vs
placebo + SOC
Oral semaglutide vs
placebo
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 with 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). 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:
Placebo
Population:
Drug-naive adults with T2D
Participants:
703
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:
Empagliflozin 25 mg
Population:
T2D patients on metformin only
Participants:
822
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:
Sitagliptin 100 mg
Population:
T2D patients on metformin
Participants:
1864
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:
Liraglutide 1.8 mg (daily subcutaneous) or placebo
Population:
T2D patients on metformin
Participants:
711
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:
Sitagliptin 100 mg
Population:
T2D patients inadequately controlled on 1-2 oral antidiabetics
Participants:
504
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:
Placebo
Population:
T2D patients using insulin with or without metformin
Participants:
731
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:
Placebo
Population:
T2D patients with high cardiovascular risk
Participants:
3183
Duration:
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:
Placebo
Population:
T2D patients with moderate renal impairment
Participants:
326
Duration:
26 weeks
RYBELSUS® [summary of product characteristics]. Bagsværd, Denmark: Novo Nordisk A/ S; March 2024.
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.
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.
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.
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.
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.
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.
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.
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.
The information contained in this site is intended for healthcare professionals only outside of the United States of America. This site is not intended to provide medical advice and/or treatment guidance. Only a physician can determine whether a specific product is correct for a particular patient. This site is not country-specific and therefore may contain information which is not applicable to your country. Novo Nordisk accepts no liability for the accuracy, completeness or use of this information, and disclaims any liability to update the information contained on this site. By accessing this site and materials you accept this legal notice and expressly confirm your status as a healthcare professional. Any images shown are models and not real patients.
The Summary of Product Characteristics (SmPC) is based on the EU SmPC as of March 2024. Registration conditions differ internationally. Always refer to the full local SmPC before prescribing.