A Trial Investigating the Effect of Semaglutide on Hypoglycaemic Counterregulation Compared to Placebo in Subjects With Type 2 Diabetes

Study Overview
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Brief Summary
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This trial is conducted in Europe. The aim of this trial is to investigate the effect of semaglutide on hypoglycaemic counter-regulation compared to placebo in subjects with type 2 diabetes.

Official Title
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A Randomised, Single-centre, Double-blind, Cross-over Trial Investigating the Effect of Semaglutide on Hypoglycaemic Counter-regulation Compared to Placebo in 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: Subjects diagnosed with type 2 diabetes and on stable treatment for a period of 90 days prior to screening with metformin as monotherapy. Stable is defined as unchanged dose Male or female, age between18-64 years (both inclusive) at the time of signing informed consent Body Mass Index (BMI) between 20.0-35.0 kg/m^2 (both inclusive) HbA1c (glycosylated haemoglobin) between 6.5-10.0% (both inclusive) Exclusion Criteria: Treatment with any glucose lowering agent(s) other than metformin in a period of 90 days before screening. An exception is short-term treatment (less than or equal to 7 days in total) with insulin in connection with intercurrent illness Recurrent severe hypoglycaemia (more than 1 severe hypoglycaemic event during the last 12 months) or hypoglycaemic unawareness as judged by the investigator or hospitalisation for diabetic ketoacidosis during the previous 6 months Blood or plasma donation within the past month or more than 500 mL within the last 3 months prior to first semaglutide dosing

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 64 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: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Semaglutide<br> | Drug: semaglutide<br>* 2 periods of 12 weeks of once weekly dosing with multiple doses of semaglutide, for subcutaneous (s.c., under the skin) injection, escalated up to 1.0 mg semaglutide. Each treatment period will be followed by a hypoglycaemic clamp<br>|
| Placebo Comparator: Placebo<br> | Drug: placebo<br>* 2 periods of 12 weeks of once weekly dosing, subcutaneous (s.c., under the skin) injection. Each treatment period will be followed by a hypoglycaemic clamp.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in mean glucagon concentration during hypoglycaemia (change from target level 5.5 mmol/L to nadir (target 2.5 mmol/L)) |  | After 12 weeks 2 days of treatment in each treatment period (Day 87 and Day 213) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in mean glucagon concentration from target level 5.5 mmol/L to 3.5 mmoL/L and from ambient plasma glucose to target levels 5.5 mmol/L, 3.5 mmol/L and nadir |  | After 12 weeks 2 days of treatment in each treatment period (Day 87 and Day 213) | 
| Change in mean concentrations of adrenaline, noradrenaline, cortisol and growth hormone from target level 5.5 mmol/L to 3.5 mmol/L and to nadir |  | After 12 weeks 2 days of treatment in each treatment period (Day 87 and Day 213) | 
| Hypoglycaemic symptoms score |  | After 12 weeks 2 days of treatment in each treatment period (Day 87 and Day 213) | 
| Time from termination of insulin infusion at nadir to reach plasma glucose level 4.0 mmol/L |  | After 12 weeks 2 days of treatment in each treatment period (Day 87 and Day 213) |