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

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

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.

Study Overview

• Status: Completed
• Conditions: Diabetes Mellitus, Type 2; Diabetes
• Intervention / Treatment: Drug: semaglutide; Drug: placebo

• Study Type: Interventional
• Enrollment (Actual): 38
• Phase: Phase 1

Contacts and Locations

Study Locations

• Austria
  • Graz, Austria, 8010
    • Novo Nordisk Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 64 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: placebo; 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.
Experimental: Semaglutide	Drug: semaglutide; 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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)

Collaborators and Investigators

• Sponsor: Novo Nordisk A/S

Publications and helpful links

General Publications

• Korsatko S, Jensen L, Brunner M, Sach-Friedl S, Tarp MD, Holst AG, Heller SR, Pieber TR. Effect of once-weekly semaglutide on the counterregulatory response to hypoglycaemia in people with type 2 diabetes: A randomized, placebo-controlled, double-blind, crossover trial. Diabetes Obes Metab. 2018 Nov;20(11):2565-2573. doi: 10.1111/dom.13422. Epub 2018 Jul 16.

Helpful Links

• Clinical Trials at Novo Nordisk

Study record dates

Study Major Dates

• Study Start (Actual): May 21, 2014
• Primary Completion (Actual): May 20, 2015
• Study Completion (Actual): May 20, 2015

Study Registration Dates

• First Submitted: May 21, 2014
• First Submitted That Met QC Criteria: May 22, 2014
• First Posted (Estimate): May 26, 2014

Study Record Updates

• Last Update Posted (Actual): August 13, 2018
• Last Update Submitted That Met QC Criteria: August 9, 2018
• Last Verified: August 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2
• Other Study ID Numbers: NN9535-3684; 2013-002751-15 (EudraCT Number); U1111-1144-7019 (Other Identifier: WHO)