Glucagon and Advanced HCL System to Prevent Exercise-Induced Hypoglycaemia in People With Type 1 Diabetes

The study consists of a screening visit (visit A) and two additional study visits (visit B and visit C) completed in a sequential order. During study visit B participants will receive s.c. administration of 150 ug glucagon prior to a 45-min moderate intensity continuous exercise session and subsequently continue into a 1-hour post-exercise observation period. During study visit C the exact same procedures will be followed with the omission of glucagon.

• GlucaGen (Drug), also known as Glucagon, GlucaGen®, Novo Nordisk, ATC code H04AA01: 150 ug glucagon will be administered to the participants before exercise.

Primary outcomes

• Difference in Percentage of Time in Target Glucose Range (PG: 3.9 - 10.0 mmol/l) During and for 1-hour After Dynamic Physical Exercise Between Visit B and C [0 min to +105 min]: This outcome measure evaluates the difference in the percentage of time participants spend within a specified glucose target range over a defined monitoring period. The measure aims to assess improvements or changes in glycemic control resulting from the intervention under study.

Secondary outcomes

• Difference in Incidence Rate of Hypoglycaemic Events (PG<3.9 mmol/l) Between Visit B and C [0 min to +105 min]: This outcome measure assesses the frequency of hypoglycemic events experienced by participants over a specified monitoring period.
• Difference in Time (Min) to Hypoglycaemia (PG<3.9 mmol/l) Between Visit B and C [0 min to +105 min]: This outcome measure evaluates the time (in minutes) taken to reach hypoglycemia during a specified monitoring period or following a specific intervention.
• Difference in Percentage of Time Below Target Glucose Range (PG<3.9 mmol/l) Between Visit B and C [0 min to +105 min]: This outcome measure evaluates the difference in the percentage of time participants spend within a specified glucose target range over a defined monitoring period. The measure aims to assess improvements or changes in glycemic control resulting from the intervention under study.
• Difference in Percentage of Time Above Target Glucose Range (PG>10.0 mmol/l) Between Visit B and C [0 min to +105 min]: This outcome measure evaluates the difference in the percentage of time participants spend within a specified glucose target range over a defined monitoring period. The measure aims to assess improvements or changes in glycemic control resulting from the intervention under study.
• Difference in Incidence Rate of Hyperglycaemia (PG>10.0 mmol/l) Between Visit B and C [0 min to +105 min]: This outcome measure assesses the incidence rate of hyperglycemia during a specified monitoring period.
• Difference in Nadir PG Concentration Between Visit B and C [0 min to +105 min]: This outcome measure assesses the difference in the lowest value of plasma glucose during a specified monitoring period.
• Difference in Peak PG Concentration Between Visit B and C [0 min to +105 min]: This outcome measure assesses the difference in peak plasma glucose during a specified monitoring period.
• Difference in Incremental Peak PG Concentration Between Visit B and C [0 min to +105 min]: This outcome measure assesses the difference in incremental peak of plasma glucose during a specified monitoring period.
• Difference in Mean PG Concentration Between Visit B and C [0 min to +105 min]: This outcome measure assesses the difference in mean plasma glucose during a specified monitoring period.
• Difference in PG Area Under the Curve (AUC) Between Visit B and C [0 min to +105 min]: This outcome measure assesses the difference in plasma glucose AUC during a specified monitoring period.
• Difference in Standard Deviation in PG Concentrations Between Visit B and C [0 min to +105 min]: This outcome measure assesses the difference in SD plasma glucose during a specified monitoring period.
• Difference in Coefficient of Variation in PG Concentrations Between Visit B and C [0 min to +105 min]: This outcome measure assesses the difference in CV in plasma glucose during a specified monitoring period.

Sex: All, ages: 18 Years to any

Inclusion Criteria:

* Age ≥ 18 years
* Type 1 diabetes ≥ 2 years
* Use of AHCL system MiniMed 780G ≥ 4 weeks
* Use of Novorapid for ≥ 1 week

Exclusion Criteria:

* Allergies to lactose or glucagon
* Known or suspected allergies to glucagon or related products
* History of hypersensitivity or allergic reaction to glucagon or lactose
* Patients with diagnosed pheochromocytoma, insulinoma or gastroparesis
* Concomitant medical or psychological conditions identified through review of medical history, physical examination and clinical laboratory analysis that, according to the investigator's assessment, makes the individual unsuitable for study participation
* Lack of compliance with key study procedures at the discretion of the investigator
* Females of childbearing potential who are pregnant, breast-feeding or intend to become pregnant or are not using adequate contraceptive methods (methods are considered adequate for study enrolment for females: an intrauterine device, hormonal contraception (birth control pills, implant, patch, vaginal ring or injection), a single partner who is sterile or infertile, or sexual abstinence. Contraception is required throughout the study duration. Sterilized or postmenopausal women (>12 months since last period) are not required to use contraception)
* Inability to understand the individual information and to give informed consent

Participant flow

Outcome results

• Difference in Percentage of Time in Target Glucose Range (PG: 3.9 - 10.0 mmol/l) During and for 1-hour After Dynamic Physical Exercise Between Visit B and C (Primary), Median, Percentage of time in range: 150 ug Glucagon Before Exercise 100 (91 to 100); Control 100 (100 to 100)
• Difference in Incidence Rate of Hypoglycaemic Events (PG<3.9 mmol/l) Between Visit B and C (Secondary), Count of participants, Participants: 150 ug Glucagon Before Exercise 0; Control 0
• Difference in Time (Min) to Hypoglycaemia (PG<3.9 mmol/l) Between Visit B and C (Secondary), Median, minutes: 150 ug Glucagon Before Exercise NA (NA to NA); Control NA (NA to NA)
• Difference in Percentage of Time Below Target Glucose Range (PG<3.9 mmol/l) Between Visit B and C (Secondary), Median, percentage of time below range: 150 ug Glucagon Before Exercise 0 (0 to 0); Control 0 (0 to 0)
• Difference in Percentage of Time Above Target Glucose Range (PG>10.0 mmol/l) Between Visit B and C (Secondary), Median, percentage of time above range: 150 ug Glucagon Before Exercise 0 (0 to 0); Control 0 (0 to 0)
• Difference in Incidence Rate of Hyperglycaemia (PG>10.0 mmol/l) Between Visit B and C (Secondary), Number, participants: 150 ug Glucagon Before Exercise 0; Control 0
• Difference in Nadir PG Concentration Between Visit B and C (Secondary), Median, mmol/l: 150 ug Glucagon Before Exercise 5.8 (5.2 to 6.9); Control 5.8 (4.9 to 6.5)
• Difference in Peak PG Concentration Between Visit B and C (Secondary), Mean, mmol/l: 150 ug Glucagon Before Exercise 9.3 +/- 1.8; Control 7.5 +/- 1.4
• Difference in Incremental Peak PG Concentration Between Visit B and C (Secondary), Median, mmol/l: 150 ug Glucagon Before Exercise 1.8 (0.9 to 2.3); Control -0.6 (-0.8 to 0.1)
• Difference in Mean PG Concentration Between Visit B and C (Secondary), Mean, mmol/l: 150 ug Glucagon Before Exercise 8.3 +/- 1.8; Control 6.7 +/- 1.3
• Difference in PG Area Under the Curve (AUC) Between Visit B and C (Secondary), Median, mmol/l*min: 150 ug Glucagon Before Exercise 824.2 (782.3 to 941.2); Control 686.2 (612.6 to 821.1)
• Difference in Standard Deviation in PG Concentrations Between Visit B and C (Secondary), Median, mmol/l: 150 ug Glucagon Before Exercise 1.0 (0.7 to 1.2); Control 0.5 (0.3 to 0.6)
• Difference in Coefficient of Variation in PG Concentrations Between Visit B and C (Secondary), Mean, Percentage of variation: 150 ug Glucagon Before Exercise 12.3 +/- 4.3; Control 7.3 +/- 2.5

Adverse events

Time frame: Fromtime 0 until time 105, the entire trial.

• Study Protocol and Statistical Analysis Plan (PDF, 2023-12-13)

• Sissel B Lundemose, MD, Principal investigator, Steno Diabetes Center Copenhagen