Micro Glucagon During Exercise in Type 1 Diabetes

Subcutaneous Dasiglucagon Use During Exercise In People With Type 1 Diabetes: Effects On Plasma Glucose And Exercise Metabolism

This proof-of-principle study to assess effects of different doses (mini and micro) of subcutaneous glucagon analog Dasiglucagon (Zealand Pharma, Copenhagen, Denmark) on the change in blood glucose concentration during moderate-intensity exercise in people with T1D.

Study Overview

• Status: Withdrawn
• Conditions: Hypoglycemia; Type 1 Diabetes
• Intervention / Treatment: Drug: Micro-glucagon; Drug: Mini-glucagon

Detailed Description

People with type 1 diabetes (T1D) are recommended to engage in regular exercise for a variety of health and fitness reasons. However, moderate-intensity exercise is associated with an increased risk of hypoglycaemia in people with T1D. Current guidelines are to reduce insulin dose and/or increase carbohydrate consumption in the context of the exercise bout. However, despite the many advances in insulin formulations and delivery devices, hypoglycaemia remains a significant risk. Mini-dose glucagon taken before an exercise bout has been shown to be an effective non-caloric strategy to prevent exercise-induced hypoglycaemia. However, even the reduced doses (150-200 µg) used in previous studies might still be rather high translating into potential side-effects (i.e. hyperglycaemia, gastrointestinal symptoms, etc.). Lower doses (below 100 µg, micro-glucagon) may be sufficiently effective to counteract hypoglycaemia risk associated with exercise and associated with better tolerance. Moreover, there is little information on the effects of subcutaneous glucagon on glycogen stores and changes in exercise metabolism. Greater understanding of exercise-associated metabolism following mini- and micro-dose glucagon using techniques such as magnetic resonance spectroscopy (MRS), continuous glucose monitoring (CGM), stable isotope tracers, and indirect calorimetry may result in novel approaches to improve blood glucose management in people with T1D. Utilising these techniques may also further our understanding of the optimal glucagon dosing (timing and amount) during exercise to manage hypoglycaemia and reduce the risk of adverse events. Proof-of-principle study to assess effects of different doses (mini and micro) of subcutaneous glucagon analog Dasiglucagon (Zealand Pharma, Copenhagen, Denmark) on the change in blood glucose concentration during moderate-intensity exercise in people with T1D. Secondly, to investigate exercise-metabolism following Dasiglucagon injection using 3 tesla magnetic resonance spectroscopy (MRS) and indirect calorimetry. Third, to assess participant experience of Dasiglucagon during exercise and the incidence of adverse events.

• Study Type: Interventional
• Phase: Early Phase 1

Contacts and Locations

• Study Contact: Name: Andreas N Melmer, MD PhD; Phone Number: +41316640249; Email: Andreas.Melmer@insel.ch

Study Locations

• Switzerland
  • Bern, Switzerland, 3010
    • Department of Diabetes, Endocrinology, Nutritional Medicine and Metabolism, Inselspital, Bern University Hospital and University of Bern, Bern, Switzerland
    • Contact: Andreas N Melmer, MD PhD; Phone Number: +41316640249; Email: Andreas.Melmer@insel.ch

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• T1D for >1 year
• Male aged 18-45 years old
• HbA1c <8.0% (64 mmol/mol) based on analysis from the central laboratory unit of Bern University Hospital
• Regular physical activity (defined as meeting 150 min moderate-intensity exercise per week)
• Using either continuous subcutaneous insulin infusion or multiple daily injections
• Written informed consent

Exclusion Criteria:

• Physical or psychological disease likely to interfere with the normal conduct of the study and interpretation of the results as judged by the investigator
• Current treatment with drugs known to interfere with metabolism e.g. systemic corticosteroids, statins, SGLT2 inhibitors, GLP1 agonists
• Relevant diabetic complications as judged by the investigator
• Body mass index 30 kg/m2
• Uncontrolled hypertension (>180/100 mmHg)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Single

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Micro-dose glucagon; 80 µg (micro-dose) subcutaneous Dasiglucagon 5 min before the start of exercise	Drug: Micro-glucagon; Administration of 80 µg (micro-dose) subcutaneous Dasiglucagon 5 min before the start of exercise; Other Names: Dasiglucagon
Experimental: Mini-dose glucagon; 150 µg mini-dose of subcutaneous Dasiglucagon 5 min before exercise the start of exercise	Drug: Mini-glucagon; Administration of 150 µg (mini-dose) subcutaneous Dasiglucagon 5 min before the start of exercise; Other Names: Dasiglucagon
No Intervention: No treatment; No treatment before the start of exercise

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to hypoglycaemia	Time (in minutes) to hypoglycaemia (plasma glucose <3.9mmol/l) during 60 minutes of aerobic exercise in individuals with type 1 diabetes using mini and micro doses of Dasiglucagon compared to no Dasiglucagon	60 minutes

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in glycaemia during exercise	Change in blood glucose concentration, calculated based on the participants' glucose at the start of exercise and the last value measured at the end of exercise. If the exercise is stopped early because of hypoglycaemia, the last exercise glucose value will be used for analysis	60 minutes
Glucose during exercise	Mean glucose concentration and area under the glucose curve during exercise	60 minutes
Glucagon during exercise	Mean glucagon concentration and area under the glucagon curve during exercise	60 minutes
Time in target	Time in target glycaemic range (4-10 mmol/L) in the recovery period and overnight	24 hours
Time in target during exercise	Time in target glycaemic range (4-10 mmol/L) during exercise	60 minutes
Hypoglycaemia	Incidence of hypoglycaemia (≤3.9 mmol/L for 15 min or more) during the 24 hour post exercise recovery period	24 hours
Glycogen content	Change in skeletal muscle and hepatic glycogen following exercise	4 hours
Any adverse events	Adverse symptoms following glucagon/placebo use	24 hours

Collaborators and Investigators

• Sponsor: Insel Gruppe AG, University Hospital Bern
• Investigators: Principal Investigator: Christoph Stettler, MD, Clinic Director

Study record dates

Study Major Dates

• Study Start (Estimated): April 1, 2023
• Primary Completion (Estimated): April 1, 2024
• Study Completion (Estimated): June 1, 2024

Study Registration Dates

• First Submitted: December 6, 2019
• First Submitted That Met QC Criteria: December 6, 2019
• First Posted (Actual): December 10, 2019

Study Record Updates

• Last Update Posted (Actual): September 1, 2023
• Last Update Submitted That Met QC Criteria: August 30, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Keywords: exercise; hypoglycemia; glucagon; type 1 diabetes; glycogen
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Immune System Diseases; Autoimmune Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 1; Hypoglycemia; Physiological Effects of Drugs; Gastrointestinal Agents; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Incretins; Glucagon; Glucagon-Like Peptide 1
• Other Study ID Numbers: GLU-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No