A Research Study to Compare Two Doses of Semaglutide Taken Once Weekly in People With Type 2 Diabetes

Study Overview
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Brief Summary
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This study compares the effect of two doses of semaglutide (1.0 mg and 2.0 mg) in people with type 2 diabetes (T2D). People taking part in the study will take the medicine together with their current diabetes medicine (sulphonylurea and/or metformin). Participants will get a dose of either 1.0 mg or 2.0 mg semaglutide once a week - which dose is decided by chance. Participants will inject semaglutide under the skin once a week. The study will last for about 49 weeks. Participants will have 9 clinic visits and 2 phone calls with the study doctor. At the visits participants will have blood taken and eye tests done. Women cannot take part if pregnant, breast-feeding or planning to become pregnant during the study period. Female participants who can get pregnant will be checked 11 times for pregnancy via urine tests.

Official Title
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Efficacy and Safety of Semaglutide 2.0 mg s.c. Once-weekly Compared to Semaglutide 1.0 mg s.c. Once-weekly in Subjects With Type 2 Diabetes

Conditions
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Diabetes Mellitus, Type 2

Intervention / Treatment
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* Drug: Semaglutide
* Drug: Placebo (semaglutide)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female, age equal to or above18 years at the time of signing informed consent Diagnosed with T2D at least 180 days prior to the day of screening HbA1c of 8-10% (64-86 mmol/mol) (both inclusive) Stable daily dose(s) for 90 days prior to the day of screening of: Any metformin formulations (equal to or above1500 mg or maximum tolerated or effective dose) alone or in combination with sulfonylureas (SU) (equal to or above half of the maximum approved dose according to local label or maximum tolerated or effective dose) Exclusion Criteria: Treatment with any medication for the indication 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, as is prior insulin treatment for gestational diabetes Renal impairment measured as estimated glomerular filtration rate (eGFR) value of <30 mL/min/1.73 m^2 according to the Chronic Kidney Disease Epidemiology Collaboration (CKDEPI) creatinine equation as defined by 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: Semaglutide 2.0 mg<br>All participants will receive one injection per week during a 12-week dose escalation period, until the target dose for semaglutide 2.0 mg is reached. From week 13 to week 40, semaglutide will be given in two weekly injections of 1.0 mg each. | Drug: Semaglutide<br>* Semaglutide injected subcutaneously (s.c., under the skin) once-weekly. Participants will keep taking their pre-study diabetes tablets throughout the study.<br>|
| Active Comparator: Semaglutide 1.0 mg<br>All participants will receive one injection per week during a 12-week dose escalation period. From week 13 to week 40, the 1.0 mg group will receive an additional injection of semaglutide placebo in order to maintain the blinding. | Drug: Semaglutide<br>* Semaglutide injected subcutaneously (s.c., under the skin) once-weekly. Participants will keep taking their pre-study diabetes tablets throughout the study.<br>Drug: Placebo (semaglutide)<br>* Semaglutide placebo injected once-weekly from week 13 to week 40.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in HbA1c | Change from baseline (week 0) to week 40 in glycosylated haemoglobin (HbA1c) was evaluated. Results are based on the 'on-treatment without rescue medication' observation period, which started at the date of first dose of trial product to either first initiation of rescue medication or the day of last dose of trial product, whichever came first; and 'In-trial' observation period which started at the date of randomisation and ended at the first of the following dates, both inclusive: end-of-treatment visit (week 40), death, participant withdrew informed consent, last contact for participant lost to follow-up. | Week 0, week 40 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Body Weight | Change from baseline (week 0) to week 40 in body weight was evaluated. Results are based on the 'on-treatment without rescue medication' observation period, which started at the date of first dose of trial product to either first initiation of rescue medication or the day of last dose of trial product, whichever came first; and 'In-trial' observation period which started at the date of randomisation and ended at the first of the following dates, both inclusive: end-of-treatment visit (week 40), death, participant withdrew informed consent, last contact for participant lost to follow-up. | Week 0, week 40 | 
| Change in Fasting Plasma Glucose (FPG) | Change from baseline (week 0) to week 40 in FPG was evaluated. Results are based on the 'on-treatment without rescue medication' observation period, which started at the date of first dose of trial product to either first initiation of rescue medication or the day of last dose of trial product, whichever came first. | Week 0, week 40 | 
| Change in Body Mass Index (BMI) | Change from baseline (week 0) to week 40 in BMI was evaluated. Results are based on the 'on-treatment without rescue medication' observation period, which started at the date of first dose of trial product to either first initiation of rescue medication or the day of last dose of trial product, whichever came first. | Week 0, week 40 | 
| Change in Waist Circumference | Change from baseline (week 0) to week 40 in waist circumference was evaluated. Results are based on the 'on-treatment without rescue medication' observation period, which started at the date of first dose of trial product to either first initiation of rescue medication or the day of last dose of trial product, whichever came first. | Week 0, week 40 | 
| Participants Who Achieved HbA1c < 7.0% | Percentage of participants who achieved HbA1c < 7.0% is presented. Results are based on the 'on-treatment without rescue medication' observation period, which started at the date of first dose of trial product to either first initiation of rescue medication or the day of last dose of trial product, whichever came first. Missing HbA1c assessment at week 40 was imputed using observed data from participants within same treatment group. | Week 40 | 
| Participants Who Achieved HbA1c ≤ 6.5% | Percentage of participants who achieved HbA1c ≤ 6.5% is presented. Results are based on the 'on-treatment without rescue medication' observation period, which started at the date of first dose of trial product to either first initiation of rescue medication or the day of last dose of trial product, whichever came first. Missing HbA1c assessment at week 40 was imputed using observed data from participants within same treatment group. | Week 40 | 
| Participants Who Achieved Weight Loss ≥5% | Percentage of participants who achieved weight loss ≥5% is presented. Results are based on the 'on-treatment without rescue medication' observation period, which started at the date of first dose of trial product to either first initiation of rescue medication or the day of last dose of trial product, whichever came first. Missing body weight assessment at week 40 was imputed using observed data from participants within same treatment group. | Week 40 | 
| Participants Who Achieved Weight Loss ≥10% | Percentage of participants who achieved weight loss ≥10% is presented. Results are based on the 'on-treatment without rescue medication' observation period, which started at the date of first dose of trial product to either first initiation of rescue medication or the day of last dose of trial product, whichever came first. Missing body weight assessment at week 40 was imputed using observed data from participants within same treatment group. | Week 40 | 
| Number of Treatment-emergent Severe or Blood Glucose (BG) Confirmed Symptomatic Hypoglycaemic Episodes | Hypoglycaemic episodes defined as treatment-emergent if the onset of the episode occurs within the on-treatment observation period. Severe or BG-confirmed symptomatic hypoglycaemia is an episode that required assistance from another person for recovery and blood glucose-confirmed by a plasma glucose value <3.1 mmol/L (56 milligrams per deciliter (mg/dL)) with symptoms consistent with hypoglycaemia. Results are based on the 'on-treatment' observation period, which started at the date of first dose of trial product and ended at the first date of any of the following: the follow-up visit (week 47), the treatment discontinuation follow-up visit (end of treatment + 7 weeks), the date of last dose of trial product +49 days or the end-date for the 'in-trial' observation period. | Week 0 to week 47 | 
| Change in Pulse Rate | Change from baseline (week 0) to week 40 in pulse rate is presented. Results are based on the 'on-treatment' observation period, which started at the date of first dose of trial product and ended at the endpoint-specific end-date. | Week 0, week 40 |