Efficacy and Safety of Semaglutide Once-weekly Versus Placebo in Drug-naïve Subjects With Type 2 Diabetes

Study Overview
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Brief Summary
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This trial is conducted globally. The aim of this trial is to investigate efficacy and safety of semaglutide once-weekly versus placebo in drug-naïve subjects with type 2 diabetes. (SUSTAIN™ 1-Monotherapy).

Official Title
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Efficacy and Safety of Semaglutide Once-weekly Versus Placebo in Drug-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: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: - For Japan only: Male or female, age above or equal to 20 years at the time of signing inform consent - Subjects diagnosed with type 2 diabetes and treated with diet and exercise for at least 30 days before screening - 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 is of child-bearing potential and 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. United Kingdom: Adequate contraceptive measures are defined as established use of oral, injected or implanted hormonal methods of contraception, placement of an intrauterine device or intrauterine system, barrier methods of contraception (condom or occlusive cap with spermicidal foam/gel/film/cream/suppository), male sterilisation (where partner is sole partner of subject), or true abstinence (when in line with preferred and usual lifestyle) - Any chronic disorder or severe disease which, in the opinion of the investigator, might jeopardise subject's safety or compliance with the protocol - Treatment with any glucose lowering agent(s) in a period of 90 days prior to screening. An exception is short-term treatment (no longer than 7 days in total) with insulin in connection with inter-current illness - History of chronic or idiopathic acute pancreatitis - Screening calcitonin value above or equal to 50 ng/L (pg/mL) - Personal or family history of medullary thyroid carcinoma or multiple endocrine neoplasia syndrome type 2 (MEN 2) - Impaired renal function defined as eGFR (estimated glomerular filtration rate ) below 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

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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Semaglutide 1.0 mg<br> | Drug: semaglutide<br>* Once weekly, administrated subcutaneously (s.c. under the skin)<br>|
| Experimental: Semaglutide 0.5 mg<br> | Drug: semaglutide<br>* Once weekly, administrated subcutaneously (s.c. under the skin)<br>|
| Placebo Comparator: Semaglutide placebo 1.0 mg<br> | Drug: placebo<br>* Once weekly, administrated subcutaneously (s.c. under the skin)<br>|
| Placebo Comparator: Semaglutide placebo 0.5 mg<br> | Drug: placebo<br>* Once weekly, administrated subcutaneously (s.c. under the skin)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in HbA1c (Glycosylated Haemoglobin) | Change from baseline (week 0) in HbA1c was evaluated after 30 weeks of treatment. Missing data were imputed from a mixed model for repeated measurements with treatment and country as fixed factors and baseline value as covariate, all nested within visit. | Week 0, week 30 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Body Weight | Change from baseline (week 0) in body weight was evaluated after 30 weeks of treatment. Missing data were imputed from a mixed model for repeated measurements with treatment and country as fixed factors and baseline value as covariate, all nested within visit. | Week 0, week 30 | 
| Change in Fasting Plasma Glucose (FPG) | Change from baseline (week 0) in FPG was evaluated after 30 weeks of treatment. Missing data were imputed from a mixed model for repeated measurements with treatment and country as fixed factors and baseline value as covariate, all nested within visit. | Week 0, week 30 | 
| Change in Systolic and Diastolic Blood Pressure | Change from baseline (week 0) in systolic and diastolic blood pressure was evaluated after 30 weeks of treatment. Missing data were imputed from a mixed model for repeated measurements with treatment and country as fixed factors and baseline value as covariate, all nested within visit. | Week 0, week 30 | 
| Subjects Who Achieve (Yes/no):HbA1c Below 7.0% (53 mmol/Mol) American Diabetes Association Target | Percentage of subjects who achieve (yes/no): HbA1c below 7.0% (53 mmol/mol) American Diabetes Association target after 30 weeks' treatment. Missing HbA1c data imputed from a mixed model for repeated measurements with treatment and country as fixed factors and baseline value as covariate, all nested within visit. | At 30 weeks of treatment | 
| Subjects Who Achieve (Yes/no):HbA1c Below or Equal to 6.5% (48 mmol/Mol) American Association of Clinical Endocrinologists Target | Percentage of subjects who achieve (yes/no): HbA1c below 6.5% (48 mmol/mol) American Diabetes Association target after 30 weeks' treatment. Missing HbA1c data imputed from a mixed model for repeated measurements with treatment and country as fixed factors and baseline value as covariate, all nested within visit. | At 30 weeks of treatment |