Phase 3
N=1,441
A Research Study Comparing a New Medicine Oral Semaglutide to Sitagliptin in People With Type 2 Diabetes
Diabetes Mellitus, Type 2
Bottom Line
View on ClinicalTrials.gov: NCT04017832 ↗Enrolled (actual)
1,441
Serious AEs
3.7%
Results posted
Sep 2023
Primary outcome: Primary: Change From Baseline to Week 26 in Glycated Haemoglobin (HbA1c) (%) — -0.8; -1.3; -1.6; -0.7 Percentage point of HbA1C — p=0.0078
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 3
- Interventions
- Oral semaglutide (Drug); Sitagliptin (Drug); Placebo (oral semaglutide) (Drug); Placebo (sitagliptin) (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Novo Nordisk A/S
- Primary completion
- Oct 2021
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Change From Baseline to Week 26 in Glycated Haemoglobin (HbA1c) (%) |
-0.8; -1.3; -1.6; -0.7; -0.8; -1.3 | 0.0078 sig |
| SECONDARY Change From Baseline to Week 26 in Fasting Plasma Glucose (FPG) |
-1.03; -1.79; -2.00; -0.52 | — |
| SECONDARY Change From Baseline to Week 26 in Self-measured Plasma Glucose (SMPG) Profile: Mean 7-point Profile |
-1.5; -2.3; -2.6; -1.2 | — |
| SECONDARY Change From Baseline to Week 26 in 7 Point SMPG Profile: Mean Postprandial Increment (Over All Meals) |
-0.4; -0.9; -1.0; -0.6 | — |
| SECONDARY Number of Participants Who Achieved HbA1c <7.0 % (53 mmol/Mol) (American Diabetes Association [ADA] Target) (Yes/no) |
139; 213; 226; 122; 182; 102 | — |
| SECONDARY Number of Participants Who Achieved HbA1c Equal to or Below 6.5 Percent (48 mmol/Mol) (American Association of Clinical Endocrinologists (AACE) Target) (Yes/no) |
81; 161; 188; 54; 240; 154 | — |
| SECONDARY Number of Participants Who Achieved HbA1c Reduction Equal to or Above 1 Percent-point (10.9 mmol/Mol) (Yes/no) |
141; 203; 226; 129; 180; 111 | — |
| SECONDARY Time to Rescue Medication |
5; 6; 6; 7 | — |
| SECONDARY Change From Baseline to Week 26 in Body Weight (Kilogram [kg]) |
-1.4; -2.9; -3.8; -0.5 | — |
| SECONDARY Percentage Change From Baseline to Week 26 in Body Weight |
-2; -4; -5; -1 | — |
| SECONDARY Change From Baseline to Week 26 in Body Mass Index (BMI) |
-0.5; -1.1; -1.4; -0.2 | — |
| SECONDARY Change From Baseline to Week 26 in Waist Circumference |
-1.6; -2.7; -3.7; -0.8 | — |
| SECONDARY Change From Baseline to Week 26 in Fasting Lipid Profile: Total Cholesterol (Ratio to Baseline) |
1.00; 0.96; 0.96; 0.99 | — |
| SECONDARY Change From Baseline to Week 26 in Fasting Lipid Profile: Low-density Lipoprotein (LDL) Cholesterol (Ratio to Baseline) |
1.02; 0.98; 0.98; 1.01 | — |
| SECONDARY Change From Baseline to Week 26 in Fasting Lipid Profile: Very-low-density Lipoprotein (VLDL) Cholesterol (Ratio to Baseline) |
1.05; 0.94; 0.94; 0.98 | — |
| SECONDARY Change From Baseline to Week 26 in Fasting Lipid Profile: High-density Lipoprotein (HDL) Cholesterol (Ratio to Baseline) |
1.02; 1.01; 1.00; 1.00 | — |
| SECONDARY Change From Baseline to Week 26 in Fasting Lipid Profile: Triglycerides (Ratio to Baseline) |
0.96; 0.86; 0.86; 0.91 | — |
| SECONDARY Change From Baseline to Week 26 in Fasting Lipid Profile: Free Fatty Acids (Ratio to Baseline) |
0.95; 0.89; 0.87; 0.96 | — |
| SECONDARY Change From Baseline to Week 26 in Short Form-36 Version 2 (SF-36v2) (Acute Version) Health Survey |
0.20; 0.48; 0.93; 0.31; -0.47; -0.41 | — |
| SECONDARY Number of Participants Who Achieved Body Weight Loss Equal to or Above 3 Percent (Yes/no) |
109; 175; 199; 68; 234; 164 | — |
| SECONDARY Number of Participants Who Achieved Body Weight Loss Equal to or Above 5 Percent (Yes/no) |
55; 107; 149; 28; 288; 235 | — |
| SECONDARY Number of Participants Who Achieved Body Weight Loss Equal to or Above 10 Percent (Yes/no) |
5; 24; 42; 2; 338; 318 | — |
| SECONDARY Number of Participants Who Achieved HbA1c Below 7.0 Percent (53 mmol/Mol) Without Hypoglycaemia (Treatment-emergent Severe or BG Confirmed Symptomatic Hypoglycaemic Episodes) and no Body Weight Gain (Yes/no) |
114; 195; 222; 79; 230; 144 | — |
| SECONDARY Number of Participants Who Achieved HbA1c Reduction Equal to or Above 1 Percent-point (10.9 mmol/Mol) and Body Weight Loss Equal to or Above 3 Percent (Yes/no) |
64; 128; 159; 33; 280; 211 | — |
| SECONDARY Number of Treatment-emergent Adverse Events During Exposure to Trial Product |
635; 741; 793; 643 | — |
| SECONDARY Number of Treatment-emergent Severe or Blood Glucose Confirmed Symptomatic Hypoglycaemic Episodes During Exposure to Trial Product |
2; 2; 2; 1 | — |
| SECONDARY Change From Baseline to Week 26 in Haematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, and Neutrophils |
0.01; 0.01; 0.00; 0.00; 0.00; 0.00 | — |
| SECONDARY Change From Baseline to Week 26 in Haematology Parameter: Haematocrit (Ratio to Baseline) |
1.01; 1.00; 1.00; 1.00 | — |
| SECONDARY Change From Baseline to Week 26 in Haematology Parameter: Haemoglobin (Ratio to Baseline) |
1.00; 1.00; 1.00; 1.00 | — |
| SECONDARY Change From Baseline to Week 26 in Haematology Parameter: Leucocytes (Ratio to Baseline) |
1.01; 1.02; 1.01; 1.04 | — |
| SECONDARY Change From Baseline to Week 26 in Haematology Parameter: Thrombocytes (Ratio to Baseline) |
0.99; 0.99; 0.99; 0.97 | — |
| SECONDARY Change From Baseline to Week 26 in Biochemistry Parameter: Calcium (Total) (Ratio to Baseline) |
0.98; 0.98; 0.99; 0.98 | — |
| SECONDARY Change From Baseline to Week 26 in Biochemistry Parameter: Potassium (Ratio to Baseline) |
1.00; 1.00; 1.00; 1.01 | — |
| SECONDARY Change From Baseline to Week 26 in Biochemistry Parameter: Sodium (Ratio to Baseline) |
1.00; 1.00; 1.00; 1.00 | — |
| SECONDARY Change From Baseline to Week 26 in Biochemistry Parameter: Urea (Ratio to Baseline) |
1.00; 0.99; 0.98; 1.03 | — |
| SECONDARY Change From Baseline to Week 26 in Biochemistry Parameter: Albumin (Ratio to Baseline) |
0.99; 0.99; 0.99; 0.99 | — |
| SECONDARY Change From Baseline to Week 26 in Calcitonin (Ratio to Baseline) |
1.00; 1.05; 1.02; 1.01 | — |
| SECONDARY Change From Baseline to Week 26 in Vital Signs: Pulse Rate |
78; 78; 78; 78 | — |
| SECONDARY Change From Baseline to Week 26 in Vital Signs: Systolic Blood Pressure |
131; 132; 130; 130 | — |
| SECONDARY Change From Baseline to Week 26 in Vital Signs: Diastolic Blood Pressure |
83; 84; 83; 83 | — |
| SECONDARY Change From Baseline to Week 26 in Electrocardiogram (ECG) Category |
174; 163; 165; 175; 21; 30 | — |
| SECONDARY Physical Examination Category |
354; 353; 355; 356; 5; 4 | — |
| SECONDARY Change From Baseline to Week 26 in Eye Examination Category |
245; 240; 254; 248; 60; 51 | — |
| SECONDARY Number of Participants With Treatment-emergent Severe or Blood Glucose Confirmed Symptomatic Hypoglycaemic Episodes During Exposure to Trial Product |
2; 2; 2; 1 | — |
Summary
This study compares 2 medicines for type 2 diabetes: oral semaglutide (a new medicine) and sitagliptin (a medicine doctors can already prescribe). Participants will either get oral semaglutide or sitagliptin - which treatment is decided by chance. Participants will get 2 tablets a day to take first thing in the morning on an empty stomach. Only 1 tablet has study medicine in it. The other tablet is a dummy medicine (placebo). After taking the semaglutide tablet, participants may not eat or drink anything for at least 30 minutes. After the 30 minutes, participants must take the sitagliptin tablet. Then participants can have their first meal of the day and take any other medicines they may need, including their metformin. The study will last for about 7 months (33 weeks). Participants will have 8 clinic visits and 1 phone call with the study doctor. At all 8 of the clinic visits, participants will have blood samples taken.
Eligibility Criteria
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 Algeria only: Male or female, age above or equal to 19 years at the time of signing informed consent.
For Taiwan only: Male or female, age above or equal to 20 years at the time of signing informed consent
- Diagnosed with type 2 diabetes mellitus 60 days or more prior to day of screening.
- HbA1c between 7.0-10.5% (53-91 mmol/mol) (both inclusive).
- Stable daily dose of metformin (equal to or above 1500 mg or maximum tolerated dose as documented in the subject medical record) 60 days or more prior to day of screening
Exclusion Criteria
- Female who is pregnant, breast-feeding or intends to become pregnant or is of child-bearing potential and not using a highly effective contraceptive method (adequate contraceptive measure as required by local regulation or practice).
- Family or personal history of multiple endocrine neoplasia type 2 (MEN 2) or medullary thyroid carcinoma (MTC). Family is defined as a first degree relative.
- History or presence of pancreatitis (acute or chronic).
- History of major surgical procedures involving the stomach potentially affecting absorption of trial product (e.g. subtotal and total gastrectomy, sleeve gastrectomy, gastric bypass surgery).
- Any of the following: myocardial infarction, stroke, hospitalization for unstable angina or transient ischaemic attack within the past 180 days prior to the day of screening and randomisation.
- 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.
- Renal impairment measured as estimated glomerular filtration rate (eGFR) below 60 mL/min/1.73 m^2 as per Chronic Kidney Disease Epidemiology Collaboration formula (CKD-EPI).
- Subjects with alanine aminotransferase (ALT) above 2.5 x upper limit of the normal (ULN).
- Uncontrolled and potentially unstable diabetic retinopathy or maculopathy. Verified by a pharmacologically pupil-dilated fundus examination performed by an ophthalmologist or another suitably qualified health care provider within the past 90 days prior to screening or in the period between screening and randomisation. Fundus examination without dilation is only allowed if the digital camera used for fundus photography has this feature.
- Presence or history of malignant neoplasms within the past 5 years prior to the day of screening. Basal and squamous cell skin cancer and any carcinoma in-situ is allowed.
Data sourced from ClinicalTrials.gov (NCT04017832). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.