Efficacy and Safety of Semaglutide Once Weekly Versus Insulin Glargine Once Daily as add-on to Metformin With or Without Sulphonylurea in Insulin-naïve Subjects With Type 2 Diabetes

Study Overview
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Brief Summary
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This trial is conducted in Africa, North and South America, Asia and Europe. The purpose of the trial is to compare the effect of once-weekly dosing of two dose levels of semaglutide versus insulin glargine once-daily on glycaemic control after 30 weeks of treatment in insulin-naïve subjects with type 2 diabetes.

Official Title
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Efficacy and Safety of Semaglutide Once Weekly Versus Insulin Glargine Once Daily as Add on to Metformin With or Without Sulphonylurea in Insulin-naïve Subjects With Type 2 Diabetes

Conditions
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Diabetes, Diabetes Mellitus, Type 2

Intervention / Treatment
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* Drug: semaglutide
* Drug: insulin glargine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female, 18 years or older at the time of signing informed consent Insulin-naïve subjects diagnosed with type 2 diabetes and on stable diabetes treatment with metformin or metformin and SU (metformin 1500 mg or higher or maximum tolerated dose and SU half of maximum allowed dose according to national label or higher) for at least 90 days before screening. Stable is defined as unchanged medication and unchanged dose HbA1c 7.0 - 10.0% (53 - 86 mmol/mol) both inclusive Exclusion Criteria: Female who is pregnant, breast-feeding or intends to become pregnant or of childbearing potential not using adequate contraceptive method (adequate contraceptive measures as required by local regulation or practice) throughout the trial including the 5 week follow-up period Any disorder which, in the opinion of the Investigator might jeopardise subject's safety or compliance with the protocol Treatment with any glucose lowering agent(s) other than stated in the inclusion criteria in a period of 90 days before screening. An exception is short-term treatment (7 days or less in total) with insulin in connection with intercurrent illness History of chronic or idiopathic acute pancreatitis Screening calcitonin value greater than or equal to 50 ng/L Personal or family history of medullary thyroid carcinoma or multiple endocrine neoplasia syndrome 2 Severe renal impairment defined as estimated glomerular filtration rate (eGFR) less than 30 mL/min/1.73 m^2 per modification of diet in renal disease (MDRD) formula (4 variable version) Acute coronary or cerebrovascular event within 90 days before randomisation Heart failure, New York Heart Association Class IV Known proliferative retinopathy or maculopathy requiring acute treatment according to the opinion of the investigator Diagnosis of malignant neoplasm in the previous 5 years (except basal cell skin cancer or squamous cell skin cancer) Mental inability, unwillingness or language barrier precluding adequate understanding of or compliance with study procedures

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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Semaglutide 0.5 mg/week<br> | Drug: semaglutide<br>* Injected subcutaneously (under the skin) once weekly. Following 4 doses (4 weeks) of 0.25 mg semaglutide weekly subjects will receive 0.5 mg semaglutide weekly for 26 weeks.<br>|
| Experimental: Semaglutide 1.0 mg/week<br> | Drug: semaglutide<br>* Injected subcutaneously (under the skin) once weekly. Following 4 doses (4 weeks) of 0.25 mg semaglutide weekly subjects will receive 0.5 mg semaglutide weekly for 26 weeks.<br>|
| Active Comparator: Insulin glargine<br> | Drug: insulin glargine<br>* Injected subcutaneously (under the skin) once daily. Subjects will start on 10 IU once daily and the dose will be adjusted according to fasting plasma glucose.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in HbA1c From Baseline | Change in HbA1c from baseline to week 30. | Week 0, week 30 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Body Weight From Baseline | Change in body weight from baseline to week 30. | Week 0, week 30 | 
| Change in Fasting Plasma Glucose From Baseline | Change in fasting plasma glucose from baseline to week 30. | Week 0, week 30 | 
| Change in Diastolic Blood Pressure. | Change in diastolic blood pressure from baseline to week 30. | Week 0, week 30 | 
| Change in Systolic Blood Pressure. | Change in systolic blood pressure from baseline to week 30. | Week 0, week 30 | 
| Change in Patient Reported Outcome (PRO) Questionnaire, Questionnaire SF-36v2™ | The Short Form (SF)-36v2™ patient reported outcomes (PRO) questionnaire was used to assess the subject's overall health related quality of life (HRQoL. PRO questionnaire (SF-36v2™) measured the HRQoL on 8 domains on individual scale ranges. The scores 0-100 (where higher scores indicated a better HRQoL) from the SF-36 were converted to a norm-based score using a T-score transformation in order to obtain a direct interpretation in relation to the distribution of the scores in the 1998 U.S. general population. The (SF-36v2™) values displayed are the estimated mean change from baseline to week 30. | Week 0, week 30 | 
| Change in Patient Reported Outcome Questionnaires. (PROs), Diabetes Treatment Satisfaction Questionnaire (DTSQs) | The Diabetes Treatment Satisfaction Questionnaire (DTSQs) questionnaire was to be used to assess a subject's treatment satisfaction. This questionnaire contained 8 components and measured the treatment for diabetes (including insulin, tablets and/or diet) in terms of convenience, flexibility and general feelings regarding treatment. The value presented is the 'Treatment Satisfaction' summary score, which is the sum of 6 of the 8 items of the DTSQs questionnaire. Response options range from 6 (best case) to 0 (worst case). Total scores for treatment satisfaction range from 0-36. Higher scores indicate higher satisfaction. The values displayed are the estimated mean change from baseline to week 30. | Week 0, week 30 | 
| Subjects Who Achieve HbA1c ≤6.5% (48 mmol/Mol), American Association of Clinical Endocrinologists (AACE) | Subjects who achieve HbA1c ≤6.5% (48 mmol/mol), American Association of Clinical Endocrinologists (AACE) after 30 weeks of treatment | After 30 weeks treatment |