Phase 3
N=521
A Research Study Comparing a New Medicine Oral Semaglutide to Placebo in People With Type 2 Diabetes
Diabetes Mellitus, Type 2
Bottom Line
View on ClinicalTrials.gov: NCT04109547 ↗Enrolled (actual)
521
Serious AEs
4.4%
Results posted
Sep 2023
Primary outcome: Primary: Change From Baseline in Glycosylated Haemoglobin (HbA1c) — -1.1; -1.5; -1.6; -0.2 Percentage of HbA1c — p=<0.0001
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 3
- Interventions
- Oral semaglutide (Drug); Placebo (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Novo Nordisk A/S
- Primary completion
- Sep 2021
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Change From Baseline in Glycosylated Haemoglobin (HbA1c) |
-1.1; -1.5; -1.6; -0.2 | <0.0001 sig |
| SECONDARY Change From Baseline in Body Weight (Kilograms [kg]) |
-1.1; -2.2; -3.1; -1.1 | — |
| SECONDARY Change From Baseline in Fasting Plasma Glucose (FPG) |
-19.07; -32.28; -32.50; 0.00 | — |
| SECONDARY Change From Baseline in Fasting 7-point Self-measured Plasma Glucose (SMPG) Profile: Mean 7-point Profile |
-29.4; -43.0; -44.5; -10.3 | — |
| SECONDARY Change From Baseline in Fasting 7-point Self-measured Plasma Glucose Profile: Mean Postprandial Increment (Over All Meals) |
-14.5; -20.0; -27.9; -6.7 | — |
| SECONDARY Change From Baseline in Body Weight (Percentage [%]) |
-1; -3; -4; -1 | — |
| SECONDARY Change From Baseline in Body Mass Index (BMI) |
-0.4; -0.8; -1.1; -0.4 | — |
| SECONDARY Change From Baseline in Waist Circumference |
-2.1; -2.2; -2.8; -1.4 | — |
| SECONDARY Change From Baseline in Fasting Lipid Profile: Total Cholesterol (Ratio to Baseline) |
0.99; 0.98; 0.94; 1.00 | — |
| SECONDARY Change From Baseline in Fasting Lipid Profile: Low-density Lipoprotein (LDL) Cholesterol (Ratio to Baseline) |
1.00; 1.00; 0.94; 1.00 | — |
| SECONDARY Change From Baseline in Fasting Lipid Profile: High-density Lipoprotein (HDL) Cholesterol (Ratio to Baseline) |
1.03; 1.02; 1.02; 1.04 | — |
| SECONDARY Change From Baseline in Fasting Lipid Profile: Triglycerides (Ratio to Baseline) |
0.96; 0.90; 0.87; 0.93 | — |
| SECONDARY Change From Baseline in Short Form-36 Version 2 (SF-36v2) (Acute Version) Health Survey |
0.25; 0.97; 0.34; 0.87; 0.34; 0.43 | — |
| SECONDARY Number of Participants Who Achieved HbA1c Less Than (<) 7.0 % (53 Millimoles Per Mole [mmol/Mol]) (American Diabetes Association (ADA) Target) (Yes/no) |
75; 100; 92; 27; 39; 17 | — |
| SECONDARY Number of Participants Who Achieved HbA1c Less Than or Equal to (<=) 6.5 Percent (48 mmol/Mol) (American Association of Clinical Endocrinologists (AACE) Target) (Yes/no) |
53; 76; 76; 12; 61; 41 | — |
| SECONDARY Number of Participants Who Achieved HbA1c Reduction Greater Than or Equal to (>=) 1 Percent (10.9 mmol/Mol) (Yes/no) |
67; 89; 87; 19; 47; 28 | — |
| SECONDARY Number of Participants Who Achieved Body Weight Loss >= 3 Percent (Yes/no) |
33; 49; 62; 28; 81; 68 | — |
| SECONDARY Number of Participants Who Achieved Body Weight Loss >= 5 Percent (Yes/no) |
17; 29; 43; 11; 98; 90 | — |
| SECONDARY Number of Participants Who Achieved Body Weight Loss >= 10 Percent (Yes/no) |
5; 7; 12; 0; 110; 112 | — |
| SECONDARY Number of Participants Who Achieved HbA1c < 7.0 Percent (53 mmol/Mol) Without Hypoglycaemia (Treatment-emergent Severe or Blood Glucose [BG] Confirmed Symptomatic Hypoglycaemic Episodes) and no Body Weight Gain (Yes/no) |
54; 80; 84; 19; 60; 37 | — |
| SECONDARY Number of Participants Who Achieved HbA1c Reduction >= 1% (10.9 mmol/Mol) and Body Weight Loss >= 3 Percent (Yes/no) |
26; 43; 53; 10; 88; 74 | — |
| SECONDARY Time From First Dose to Initiation of Rescue Medication |
NA; NA; NA | — |
| SECONDARY Semaglutide Plasma Concentrations |
4.36; 11.22; 17.71 | — |
| SECONDARY Change From Baseline in Haematology - Haematocrit (Ratio to Baseline) |
1.00; 1.00; 1.00; 1.00 | — |
| SECONDARY Change From Baseline in Haematology - Haemoglobin (Ratio to Baseline) |
1.01; 1.00; 1.00; 1.00 | — |
| SECONDARY Change From Baseline in Haematology - Leucocytes (Ratio to Baseline) |
1.03; 1.01; 1.04; 1.03 | — |
| SECONDARY Change From Baseline in Haematology - Thrombocytes (Ratio to Baseline) |
1.03; 1.01; 1.04; 1.02 | — |
| SECONDARY Change From Baseline in Haematology - Basophils, Eosinophils, Lymphocytes, Monocytes and Neutrophils |
0.00; -0.01; -0.01; -0.01; 0.01; 0.02 | — |
| SECONDARY Change From Baseline in Biochemistry - Urea (Ratio to Baseline) |
1.02; 1.00; 1.02; 1.07 | — |
| SECONDARY Change From Baseline in Biochemistry - Creatinine (Ratio to Baseline) |
1.03; 1.02; 1.03; 0.99 | — |
| SECONDARY Change From Baseline in Biochemistry - Alanine Aminotransferase (Ratio to Baseline) |
0.88; 0.89; 0.85; 0.88 | — |
| SECONDARY Change From Baseline in Biochemistry - Aspartate Aminotransferase (Ratio to Baseline) |
0.91; 0.91; 0.90; 0.89 | — |
| SECONDARY Change From Baseline in Biochemistry - Alkaline Phosphatase (Ratio to Baseline) |
0.94; 0.92; 0.95; 0.95 | — |
| SECONDARY Change From Baseline in Biochemistry - Total Bilirubin (Ratio to Baseline) |
0.89; 0.84; 0.85; 0.95 | — |
| SECONDARY Change From Baseline in Biochemistry - Amylase (Ratio to Baseline) |
1.09; 1.20; 1.11; 1.05 | — |
| SECONDARY Change From Baseline in Biochemistry - Lipase (Ratio to Baseline) |
1.24; 1.60; 1.35; 1.05 | — |
| SECONDARY Change From Baseline in Biochemistry - Creatine Kinase (Ratio to Baseline) |
1.06; 0.96; 1.00; 0.93 | — |
| SECONDARY Change From Baseline in Calcium (Ratio to Baseline) |
0.98; 0.97; 0.98; 0.97 | — |
| SECONDARY Change From Baseline in Potassium (Ratio to Baseline) |
1.02; 1.01; 1.00; 1.01 | — |
| SECONDARY Change From Baseline in Sodium (Ratio to Baseline) |
1.00; 1.00; 1.00; 1.00 | — |
| SECONDARY Change From Baseline in Albumin (Ratio to Baseline) |
1.00; 0.99; 0.99; 0.99 | — |
| SECONDARY Change From Baseline in Calcitonin (Ratio to Baseline) |
1.01; 1.09; 1.15; 0.98 | — |
| SECONDARY Change From Baseline in Pulse Rate |
2; 4; 5; 1 | — |
| SECONDARY Change From Baseline in Systolic Blood Pressure |
1; -2; -4; -2 | — |
| SECONDARY Change From Baseline in Diastolic Blood Pressure |
0; -1; -2; -2 | — |
| SECONDARY Change From Baseline in Electrocardiogram (ECG) Category |
53; 61; 59; 58; 12; 11 | — |
| SECONDARY Change From Baseline in Physical Examination Category |
113; 118; 115; 115; 0; 0 | — |
| SECONDARY Change From Baseline in Eye Examination Category |
73; 77; 83; 75; 6; 5 | — |
| SECONDARY Number of Treatment-emergent Adverse Events (TEAEs) |
251; 292; 231; 212 | — |
| SECONDARY Number of Treatment-emergent Severe or Blood Glucose (BG) Confirmed Symptomatic Hypoglycaemic Episodes |
0; 0; 0; 0 | — |
| SECONDARY Number of Participants With Treatment-emergent Severe or BG Confirmed Symptomatic Hypoglycaemic Episodes |
0; 0; 0; 0 | — |
| SECONDARY Anti-semaglutide Binding Antibody Levels |
2.1 | — |
| SECONDARY Number of Participants With Anti-semaglutide Binding Antibodies |
0; 1; 0 | — |
| SECONDARY Number of Participants With Anti-semaglutide Binding Antibodies Cross Reacting With Native GLP-1 |
0; 0; 0 | — |
Summary
The study compares 2 medicines for type 2 diabetes: oral semaglutide (a new medicine) and placebo (a dummy medicine). Researchers will test semaglutide to see how well it works compared to placebo. The study will also test if semaglutide is safe. Participants will either get semaglutide or placebo - which treatment is decided by chance. Participants will get 1 tablet a day to take with up to half a glass of water. Participants must take the tablet first thing in the morning on an empty stomach. After taking the tablet, participants must not eat or drink anything for at least 30 minutes. After the 30 minutes, participants can have their first meal of the day and take any other medicines they may need. The study will last for about 8 months (36 weeks). Participants will have 9 clinic visits and 2 phone calls with the study doctor. At all 9 of the clinic visits, participants will have blood samples taken. At 5 of the clinic visits, participants must arrive fasting. This means they cannot eat for 8 hours before the visit. It is fine to drink water up to 2 hours before the visit. This is for some of the blood samples that will be taken at the visit. Women cannot take part if pregnant, breastfeeding or planning to become pregnant during the study period.
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 the informed consent.
For Taiwan only: Male or female, age above or equal to 20 years at the time of signing the informed consent.
- Diagnosed with type 2 diabetes mellitus
- HbA1c between 7.0 -10.0% (53-86 mmol/mol) (both inclusive).
Exclusion Criteria
- - Female who is pregnant, breast-feeding or intends to become pregnant or is of child-bearing potential and not using an highly effective contraceptive method.
- 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.
- 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).
- 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 (NCT04109547). 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.