Research Study to Compare Three Doses of Semaglutide Tablets Taken Once Daily in People With Type 2 Diabetes

Study Overview
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Brief Summary
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This study compares three doses of once daily semaglutide tablets in people with type 2 diabetes who were previously treated with other oral anti-diabetic medicines. Participants will be initiated on the lowest starting dose of 3 mg and gradually increased until they reach the final trial dose of 14 mg, 25 mg or 50 mg once daily semaglutide tablets. The final three doses will be randomized (i.e., decided by chance). Participants will be administered one tablet per day for 68 weeks. Women cannot take part if they are pregnant, breast-feeding or planning to become pregnant during the study period. Women who can get pregnant will be checked for pregnancy via urine tests. Once daily semaglutide tablets (3 mg, 7 mg and 14 mg) are approved for the treatment of type 2 diabetes in the US, in the EU and in some other countries, under the brand name Rybelsus®.

Official Title
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Efficacy and Safety of Once-daily Oral Semaglutide 25 mg and 50 mg Compared With 14 mg in Subjects With Type 2 Diabetes

Conditions
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Diabetes Mellitus, Type 2

Intervention / Treatment
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* Drug: Oral semaglutide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female, age above or equal to 18 years at the time of signing informed consent. Diagnosed with type 2 diabetes mellitus at least 180 days prior to the day of screening. HbA1c of 8.0-10.5% (64-91 mmol/mol) (both inclusive). BMI equal to or above 25 kg/m^2 Stable daily dose(s) for 90 days prior to the day of screening of any of the following treatment regimens: No more than 3 of the following oral anti-diabetic drugs and at least 1 marked with a *: Metformin (equal to or above1500 mg or maximum tolerated or effective dose). Sulfonylureas (SU) (equal to or above half of the maximum approved dose according to local label or maximum tolerated or effective dose). Sodium/glucose cotransporter 2 (SGLT2) inhibitors (maximum tolerated dose). Dipeptidyl peptidase-4 (DPP-4) inhibitors (maximally indicated dose as per local label). Subjects, on treatment with stable dose of DPP-4 inhibitors at inclusion, must be willing to discontinue DPP-4 inhibitor treatment at randomisation (with no wash-out). Exclusion Criteria: Treatment with any medication indicated for the treatment of diabetes or obesity other than stated in the inclusion criteria within the past 90 days prior to the day of screening. However, short term insulin treatment for a maximum of 14 days prior to the day of screening is allowed. Renal impairment measured as estimated glomerular filtration rate (eGFR) value of below 30 mL/min/1.73 m^2 according to Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) creatinine equation as defined by kidney disease improving global outcomes (KDIGO 2012) classification. Uncontrolled and potentially unstable diabetic retinopathy or maculopathy. Verified by a fundus examination performed within the past 90 days prior to 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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Oral semaglutide 50 mg<br>Participants will receive once daily semaglutide tablets in a dose escalating manner for 68 weeks: 3 mg (week 1-4), 7 mg (week 5-8), 14 mg (week 9-12), 25 mg (week 13-16) and 50 mg (week 17-68). | Drug: Oral semaglutide<br>* Participants will receive once daily semaglutide tablets (oral administration) in a dose escalating manner for 68 weeks.<br>|
| Experimental: Oral semaglutide 25 mg<br>Participants will receive once daily semaglutide tablets in a dose escalating manner for 68 weeks: 3 mg (week 1-4), 7 mg (week 5-8), 14 mg (week 9-12) and 25 mg (week 13-68). | Drug: Oral semaglutide<br>* Participants will receive once daily semaglutide tablets (oral administration) in a dose escalating manner for 68 weeks.<br>|
| Active Comparator: Oral semaglutide 14 mg<br>Participants will receive once daily semaglutide tablets in a dose escalating manner for 68 weeks: 3 mg (week 1-4), 7 mg (week 5-8) and 14 mg (week 9-68). | Drug: Oral semaglutide<br>* Participants will receive once daily semaglutide tablets (oral administration) in a dose escalating manner for 68 weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in glycated haemoglobin (HbA1c) | %-point | From baseline (week 0) to week 52 | 
| Change in HbA1c | %-point | From baseline (week 0) to week 68 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in body weight | kg | From baseline (week 0) to week 52 | 
| Change in body weight | kg | From baseline (week 0) to week 68 | 
| Change in fasting plasma glucose (FPG) | Millimoles per liter (mmol/L). | From baseline (week 0) to week 52 | 
| Change in FPG | mmol/L | From baseline (week 0) to week 68 | 
| Change in BMI | Kilograms per meter square (kg/m^2) | From baseline (week 0) to week 52 | 
| Change in BMI | Kilograms per meter square (kg/m^2) | From baseline (week 0) to week 68 | 
| Achievement of HbA1c below 7% (Yes/No) | Count of participants | At week 52 | 
| Achievement of HbA1c below 7% (Yes/No) | Count of participants | At week 68 | 
| Achievement of HbA1c equal to or below 6.5% (Yes/No) | Count of participants | At week 52 | 
| Achievement of HbA1c equal to or below 6.5% (Yes/No) | Count of participants | At week 68 | 
| Relative change in body weight | Percentage (%) | From baseline (week 0) to week 52 | 
| Relative change in body weight | Percentage (%) | From baseline (week 0) to week 68 | 
| Change in waist circumference | centimeters (cm) | From baseline (week 0) to week 52 | 
| Change in waist circumference | cm | From baseline (week 0) to week 68 | 
| Achievement of weight loss equal to or above 5% (Yes/No) | Count of participants | At week 52 | 
| Achievement of weight loss equal to or above 5% (Yes/No) | Count of participants | At week 68 | 
| Achievement of weight loss equal to or above 10% (Yes/No) | Count of participants | At week 52 | 
| Achievement of weight loss equal to or above 10% (Yes/No) | Count of participants | At week 68 | 
| Adverse events | Count of events | From baseline (week 0) to follow-up visit (week 73) | 
| Change in fasting lipid profiles: total cholesterol, low density lipoprotein (LDL) cholesterol, high density lipoprotein (HDL) cholesterol, triglycerides | mmol/L | From baseline (week 0) to week 52 | 
| Change in fasting lipid profiles: total cholesterol, low density lipoprotein (LDL) cholesterol, high density lipoprotein (HDL) cholesterol, triglycerides | milligrams per deciliter (mg/dL) | From baseline (week 0) to week 52 | 
| Change in fasting lipid profiles: total cholesterol, low density lipoprotein (LDL) cholesterol, high density lipoprotein (HDL) cholesterol, triglycerides | mmol/L | From baseline (week 0) to week 68 | 
| Change in fasting lipid profiles: total cholesterol, low density lipoprotein (LDL) cholesterol, high density lipoprotein (HDL) cholesterol, triglycerides | mg/dL | From baseline (week 0) to week 68 | 
| Change in pulse | Beats per minute (beats/min) | From baseline (week 0) to week 52 | 
| Change in pulse | beats/min | From baseline (week 0) to week 68 | 
| Change in systolic blood pressure | millimeters of mercury (mmHg) | Fron baseline (week 0) to week 52 | 
| Change in systolic blood pressure | mmHg | Fron baseline (week 0) to week 68 | 
| Change in diastolic blood pressure | mmHg | Fron baseline (week 0) to week 52 | 
| Change in diastolic blood pressure | mmHg | Fron baseline (week 0) to week 68 |