Efficacy and Safety of Oral Semaglutide Versus Liraglutide and Versus Placebo in Subjects With Type 2 Diabetes Mellitus (PIONEER 4)

Novo Nordisk

Status and phase: Completed; Phase 3

Conditions: Diabetes; Diabetes Mellitus, Type 2

Treatments: Drug: placebo; Drug: semaglutide; Drug: liraglutide

Study type: Interventional

Funder types: Industry

Identifiers

NCT02863419

U1111-1176-6029 (Other Identifier)

2015-005210-30 (EudraCT Number)

NN9924-4224

Details and patient eligibility

About

This trial is conducted globally. The aim of this trial is to investigate efficacy and safety of oral Semaglutide versus Liraglutide and versus Placebo in Subjects with Type 2 Diabetes Mellitus.

Enrollment: 711 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Informed consent obtained before any trial-related activities. Trial-related activities are any procedures that are carried out as part of the trial, including activities to determine suitability for the trial
• Male or female, age above or equal to 18 years at the time of signing informed consent. For Japan only: Male or female, age at least 20 years at the time of signing informed consent
• Diagnosed with type 2 diabetes mellitus for at least 90 days prior to day of screening.
• HbA1c (glycosylated haemoglobin) of 7.0-9.5 % (53-80.3 mmol/mol) (both inclusive)
• Stable daily dose of metformin (above or equal to 1500 mg or maximum tolerated dose as documented in the subject medical record) alone or in combination with a stable daily dose of a SGLT-2 (sodium-glucose co-transporter-2) inhibitor for at least 90 days prior to day of screening (fixed-dose combinations are allowed)

Exclusion criteria

• Female who is pregnant, breast-feeding or intends to become pregnant or is of child-bearing potential and not using an adequate contraceptive method (adequate contraceptive measure as required by local regulation or practice).For certain specific countries: Additional specific requirements apply
• Any disorder, which in the investigator's opinion might jeopardise subject's safety or compliance with the protocol
• Family or personal history of Multiple Endocrine Neoplasia Type 2 (MEN 2) or Medullary Thyroid Carcinoma (MTC)
• History of pancreatitis (acute or chronic)
• History of major surgical procedures involving the stomach and potentially affecting absorption of trial product (e.g. subtotal and total gastrectomy, sleeve gastrectomy, gastric bypass surgery)
• Any of the following: myocardial infarction (MI), stroke or hospitalisation for unstable angina or transient ischaemic attack within the past 180 days prior to the day of screening
• Subjects presently classified as being in New York Heart Association (NYHA) Class IV
• Planned coronary, carotid or peripheral artery revascularisation known on the day of screening
• Subjects with ALT (alanine aminotransferase) above 2.5 × upper normal limit (UNL)
• Renal impairment defined as estimated Glomerular Filtration Rate (eGFR) below 60 mL/min/1.73 m^2 as per Chronic Kidney Disease Epidemiology Collaboration formula (CKD-EPI)
• Treatment with any medication for the indication of diabetes or obesity other than stated in the inclusion criteria in a period of 90 days before the day of screening. An exception is short-term insulin treatment for acute illness for a total of below or equal to 14 days
• Proliferative retinopathy or maculopathy requiring acute treatment. Verified by fundus photography or dilated fundoscopy performed within 90 days prior to randomisation
• History or presence of malignant neoplasms within the last 5 years (except basal and squamous cell skin cancer and carcinoma in situ)
• History of diabetic ketoacidosis

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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711 participants in 3 patient groups, including a placebo group

Oral Semaglutide

Experimental group

Treatment:

Drug: semaglutide

Liraglutide

Active Comparator group

Treatment:

Drug: liraglutide

Placebo

Placebo Comparator group

Treatment:

Drug: placebo