Research Study to Compare Semaglutide Tablets With Empagliflozin Tablets Taken Once Daily in People With Type 2 Diabetes and Obesity (PIONEER START)
Primary Purpose
Diabetes Mellitus, Type 2
Status
Withdrawn
Phase
Phase 3
Locations
Study Type
Interventional
Intervention
Semaglutide
Empagliflozin
Sponsored by

About this trial
This is an interventional treatment trial for Diabetes Mellitus, Type 2
Eligibility Criteria
Inclusion Criteria:
- Male or female, age 18- less than (<) 50 years at the time of signing informed consent.
- Diagnosed with type 2 diabetes mellitus less than or equal to (<=) 365 days from the day of screening.
- Glycated haemoglobin (HbA1c) of 7.0-9.5 percentage (%) (53-80 millimoles per milliliter [mmol/mol]) (both inclusive).
- Body mass index (BMI) greater than or equal to (>=) 30.0 kilograms per meter square (kg/m^2).
- Treatment naïve to any antidiabetic drug(s). However, for a subset of participants (≤25%) any metformin dose or formulations administered is allowed.
Exclusion Criteria:
- Treatment with any medication for the indication of diabetes or obesity other than stated in the inclusion criteria since diagnosed with type 2 diabetes mellitus. Prior insulin treatment for gestational diabetes is allowed.
- Renal impairment measured as estimated glomerular filtration rate (eGFR) value of less than (<) 60 milliliter per minute per 1.73 meter square (1.7mL/min/1.73 m^2) at screening.
- Uncontrolled and potentially unstable diabetic retinopathy or maculopathy. Verified by a fundus examination performed within the past 90 days prior to day of screening or in the period between screening and randomisation. Pharmacological pupil-dilation is a requirement unless using a digital fundus photography camera specified for non-dilated examination.
- C-peptide less than (<)1.5 nanograms per milliliter (ng/mL) at screening.
- Positive insulinoma associated-protein 2 (IA-2) antibodies or anti-glutamic acid decarboxylase (anti-GAD) antibodies.
- History of major surgical procedures involving the stomach or small intestine potentially affecting absorption of drugs and/or nutrients.
- Presence of clinically significant gastrointestinal disorders potentially affecting absorption of drugs and/or nutrients, as judged by the investigator.
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
Oral semaglutide
Empagliflozin
Arm Description
Participants will receive once daily oral semaglutide tablet for 104 weeks in a dose escalation fashion of 3milligrams (mg), 7mg, 14 mg and 25 mg once every four weeks during the first 16 weeks and a maintenance dose of 55 mg for the rest 88 weeks.
Participants will receive once daily empagliflozin tablet for up to 104 weeks, starting with a dose of 10 mg for the first 8 weeks and the maintenance dose of 25 mg for the rest 96 weeks.
Outcomes
Primary Outcome Measures
Participants acheiving glycated haemoglobin (HbA1c) less than (<) 7 percentage (%) (Yes/No)
Measured as count of participants.
Participants acheiving body weight reduction greater than or equal to (>=) 5% (Yes/No)
Measured as count of participants.
Secondary Outcome Measures
Change in HbA1c
Measured as percentage (%)-point.
Change in fasting plasma glucose (FPG)
Measured in millimoles per liter (mmol/l).
Change in self-measured plasma glucose (SPMG) 7-point mean profile
Measured in millimoles per liter(mmol/l).
Change in self-measured plasma glucose (SPMG) mean post prandial increments
Measured in millimoles per liter(mmol/l).
Time to additional anti-diabetic medication
Measured in days.
Change in body weight
Measured in kilograms (kg).
Relative change in body weight
Measured as percentage (%).
Change in waist circumference
Measured in centimeters (cm).
Participants achieving glycated haemoglobin (HbA1c) less than or equal to (<=) 6.5% (Yes/No)
Measured as count of participants.
Participants achieving glycated haemoglobin (HbA1c) reduction greater than or equal to (>=) 0.7%-point (Yes/No)
Measured as count of participants.
Participants achieving body weight reduction greater than or equal to (>=) 5 percentage (%)
Measured as count of participants.
Change in systolic blood pressure
Measured in millimiters of mercury (mmHg).
Change in total cholesterol
Measured as ratio to baseline.
Change in high density lipoprotein (HDL)
Measured as ratio to baseline.
Change in low density lipoprotein (LDL)
Measured as ratio to baseline.
Change in very low density lipoprotein (VLDL)
Measured as ratio to baseline.
Change in Triglycerides
Measured as ratio to baseline.
Change in free fatty acids
Measured as ratio to baseline.
Number of treatment emergent adverse events
Measured as count of events.
Change in Control of Eating Questionnaire (CoEQ) score - Craving Control domain
Measured as score on a scale. Scales range from 0 (minimum) to 10 (maximum).
Change in Control of Eating Questionnaire (CoEQ) score - Craving for Savory domaina
Measured as score on a scale. Scales range from 0 (minimum) to 10(maximum).
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT05444153
Brief Title
Research Study to Compare Semaglutide Tablets With Empagliflozin Tablets Taken Once Daily in People With Type 2 Diabetes and Obesity
Acronym
PIONEER START
Official Title
Efficacy and Safety of Early Initiation of Oral Semaglutide 50 mg Once Daily Versus Empagliflozin 25 mg Once Daily in Younger Patients With Newly Diagnosed Type 2 Diabetes and Obesity
Study Type
Interventional
2. Study Status
Record Verification Date
November 2022
Overall Recruitment Status
Withdrawn
Why Stopped
Sponsor decision
Study Start Date
October 6, 2022 (Anticipated)
Primary Completion Date
October 2, 2024 (Anticipated)
Study Completion Date
August 29, 2025 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Novo Nordisk A/S
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
This study compares the medicines semaglutide and empagliflozin in people with newly diagnosed type 2 diabetes and obesity. The study will look mainly at how well the blood sugar and body weight are controlled when participants are taking the study medicine. Participants will either get semaglutide tablets or empagliflozin tablets. Which treatment participants get is decided by chance. Participants will get one tablet per day for 2 years. The study will last for about 2 years and 8 weeks.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Diabetes Mellitus, Type 2
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
0 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Oral semaglutide
Arm Type
Experimental
Arm Description
Participants will receive once daily oral semaglutide tablet for 104 weeks in a dose escalation fashion of 3milligrams (mg), 7mg, 14 mg and 25 mg once every four weeks during the first 16 weeks and a maintenance dose of 55 mg for the rest 88 weeks.
Arm Title
Empagliflozin
Arm Type
Active Comparator
Arm Description
Participants will receive once daily empagliflozin tablet for up to 104 weeks, starting with a dose of 10 mg for the first 8 weeks and the maintenance dose of 25 mg for the rest 96 weeks.
Intervention Type
Drug
Intervention Name(s)
Semaglutide
Intervention Description
Participants will receive 1 tablet of oral semaglutide once daily.
Intervention Type
Drug
Intervention Name(s)
Empagliflozin
Intervention Description
Participants will receive 1 tablet of empagliflozin once daily.
Primary Outcome Measure Information:
Title
Participants acheiving glycated haemoglobin (HbA1c) less than (<) 7 percentage (%) (Yes/No)
Description
Measured as count of participants.
Time Frame
At week 104
Title
Participants acheiving body weight reduction greater than or equal to (>=) 5% (Yes/No)
Description
Measured as count of participants.
Time Frame
At week 104
Secondary Outcome Measure Information:
Title
Change in HbA1c
Description
Measured as percentage (%)-point.
Time Frame
From randomisation (week 0) to week 104
Title
Change in fasting plasma glucose (FPG)
Description
Measured in millimoles per liter (mmol/l).
Time Frame
From randomisation (week 0) to week 104
Title
Change in self-measured plasma glucose (SPMG) 7-point mean profile
Description
Measured in millimoles per liter(mmol/l).
Time Frame
From randomisation (week 0) to week 104
Title
Change in self-measured plasma glucose (SPMG) mean post prandial increments
Description
Measured in millimoles per liter(mmol/l).
Time Frame
From randomisation (week 0) to week 104
Title
Time to additional anti-diabetic medication
Description
Measured in days.
Time Frame
From randomisation (week 0) to week 104
Title
Change in body weight
Description
Measured in kilograms (kg).
Time Frame
From randomisation (week 0) to week 104
Title
Relative change in body weight
Description
Measured as percentage (%).
Time Frame
From randomisation (week 0) to week 104
Title
Change in waist circumference
Description
Measured in centimeters (cm).
Time Frame
From randomisation (week 0) to week 104
Title
Participants achieving glycated haemoglobin (HbA1c) less than or equal to (<=) 6.5% (Yes/No)
Description
Measured as count of participants.
Time Frame
From randomisation (week 0) to week 104
Title
Participants achieving glycated haemoglobin (HbA1c) reduction greater than or equal to (>=) 0.7%-point (Yes/No)
Description
Measured as count of participants.
Time Frame
From randomisation (week 0) to week 104
Title
Participants achieving body weight reduction greater than or equal to (>=) 5 percentage (%)
Description
Measured as count of participants.
Time Frame
From randomisation (week 0) to week 104
Title
Change in systolic blood pressure
Description
Measured in millimiters of mercury (mmHg).
Time Frame
From randomisation (week 0) to week 104
Title
Change in total cholesterol
Description
Measured as ratio to baseline.
Time Frame
From randomisation (week 0) to week 104
Title
Change in high density lipoprotein (HDL)
Description
Measured as ratio to baseline.
Time Frame
From randomisation (week 0) to week 104
Title
Change in low density lipoprotein (LDL)
Description
Measured as ratio to baseline.
Time Frame
From randomisation (week 0) to week 104
Title
Change in very low density lipoprotein (VLDL)
Description
Measured as ratio to baseline.
Time Frame
From randomisation (week 0) to week 104
Title
Change in Triglycerides
Description
Measured as ratio to baseline.
Time Frame
From randomisation (week 0) to week 104
Title
Change in free fatty acids
Description
Measured as ratio to baseline.
Time Frame
From randomisation (week 0) to week 104
Title
Number of treatment emergent adverse events
Description
Measured as count of events.
Time Frame
From randomisation (week 0) to week 109
Title
Change in Control of Eating Questionnaire (CoEQ) score - Craving Control domain
Description
Measured as score on a scale. Scales range from 0 (minimum) to 10 (maximum).
Time Frame
From randomisation (week 0) to week 104
Title
Change in Control of Eating Questionnaire (CoEQ) score - Craving for Savory domaina
Description
Measured as score on a scale. Scales range from 0 (minimum) to 10(maximum).
Time Frame
From randomisation (week 0) to week 104
10. Eligibility
Sex
All
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Male or female, age 18- less than (<) 50 years at the time of signing informed consent.
Diagnosed with type 2 diabetes mellitus less than or equal to (<=) 365 days from the day of screening.
Glycated haemoglobin (HbA1c) of 7.0-9.5 percentage (%) (53-80 millimoles per milliliter [mmol/mol]) (both inclusive).
Body mass index (BMI) greater than or equal to (>=) 30.0 kilograms per meter square (kg/m^2).
Treatment naïve to any antidiabetic drug(s). However, for a subset of participants (≤25%) any metformin dose or formulations administered is allowed.
Exclusion Criteria:
Treatment with any medication for the indication of diabetes or obesity other than stated in the inclusion criteria since diagnosed with type 2 diabetes mellitus. Prior insulin treatment for gestational diabetes is allowed.
Renal impairment measured as estimated glomerular filtration rate (eGFR) value of less than (<) 60 milliliter per minute per 1.73 meter square (1.7mL/min/1.73 m^2) at screening.
Uncontrolled and potentially unstable diabetic retinopathy or maculopathy. Verified by a fundus examination performed within the past 90 days prior to day of screening or in the period between screening and randomisation. Pharmacological pupil-dilation is a requirement unless using a digital fundus photography camera specified for non-dilated examination.
C-peptide less than (<)1.5 nanograms per milliliter (ng/mL) at screening.
Positive insulinoma associated-protein 2 (IA-2) antibodies or anti-glutamic acid decarboxylase (anti-GAD) antibodies.
History of major surgical procedures involving the stomach or small intestine potentially affecting absorption of drugs and/or nutrients.
Presence of clinically significant gastrointestinal disorders potentially affecting absorption of drugs and/or nutrients, as judged by the investigator.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clinical Transparency dept. 2834
Organizational Affiliation
Novo Nordisk A/S
Official's Role
Study Director
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
According to the Novo Nordisk disclosure commitment on novonordisk-trials.com.
IPD Sharing URL
http://novonordisk-trials.com
Learn more about this trial
Research Study to Compare Semaglutide Tablets With Empagliflozin Tablets Taken Once Daily in People With Type 2 Diabetes and Obesity
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