The Postprandial Hypo-Avoid Study

Low-Dose Glucagon and Automated Insulin Delivery for Prevention of Spontaneous Exercise-Induced Hypoglycemia in People With Type 1 Diabetes

The objective of the study is to evaluate whether pre-exercise administration of low-dose subcutaneous glucagon prevents or attenuates exercise-induced declines in plasma glucose concentration during and after moderate-intensity continuous exercise (MICE) performed approximately 90 minutes after a meal in adults with type 1 diabetes using an automated insulin delivery (AID) system.

The primary endpoint is the difference in the change in plasma glucose (PG) from exercise initiation to the nadir during exercise and through the 2-hour post-exercise period between the glucagon (GCN) and carbohydrate (CHO) visits.

Study Overview

• Status: Not yet recruiting
• Conditions: Type 1 Diabetes Mellitus
• Intervention / Treatment: Drug: Low-Dose Glucagon; Dietary supplement: Glucose Arm

Detailed Description

This is a randomized, non-blinded, two-period crossover study including 18 adults with type 1 diabetes using an EU-approved automated insulin delivery (AID) system. Each participant will attend one screening visit followed by two experimental visits performed in random order, separated by at least seven days.

Eligible participants are adults (≥18 years) with type 1 diabetes for at least 2 years, using an automated insulin delivery system for ≥3 months, treated with NovoRapid or Fiasp for at least 1 week prior to enrollment, and proficient in carbohydrate counting.

At each experimental visit, participants will perform a standardized bout of MICE approximately 90 minutes after a meal. On one visit, a low-dose glucagon injection will be administered immediately before exercise; on the other, 20 g oral glucose tablets will be consumed. Right before exercise, the AID system's higher glucose target/exercise mode will be activated and will remain active until 15 minutes after exercise.

• Study Type: Interventional
• Enrollment (Estimated): 18
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Emilie Lindkvist, MD, PhD Candidate; Phone Number: +45 21563054; Email: emilie.lindkvist@regionh.dk
• Study Contact Backup: Name: Sissel Lundemose, MD, PhD; Phone Number: +4523742764; Email: sissel.lundemose@regionh.dk

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age ≥ 18 years
• Type 1 diabetes ≥ 2 years
• Using an automated insulin delivery system for ≥ 3 months
• NovoRapid or Fiasp use ≥1 week
• Proficiency in carbohydrate counting

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Visit GCN; Plasma and sensor glucose are monitored before, during, and after a bout of moderate-intensity exercise shortly after consumption of a meal. Before exercise initiation, participants will be given low-dose glucagon to prevent hypoglycemia.	Drug: Low-Dose Glucagon; Participants will be given a low-dose of glucagon before starting the exercise session
Active Comparator: Visit CHO; Plasma and sensor glucose are monitored before, during, and after a bout of moderate-intensity exercise shortly after consumption of a meal. Before exercise initiation, participants will be given a dose of glucose to prevent hypoglycemia.	Dietary supplement: Glucose Arm; Participants will be given a dose of glucose before starting exercise

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change in plasma glucose (PG) from exercise initiation to the nadir during exercise and throughout the 2-hour post-exercise period between visit GCN and CHO	From exercise initiation until two hours following exercise

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent PG time in range (3.9-10.0 mmol/L) between visits GCN and CHO		From exercise onset to +120 min
Incidence of hypoglycemia (PG <3.9 mmol/L) between visits GCN and CHO	Binary	0-180 min
Time to hypoglycemia (PG <3.9 mmol/L) between visits GCN and CHO		0-180 min
Percent time below range (PG <3.9 mmol/L) between visit GCN and CHO		0-180 mins
Percent time above range (PG >10.0 mmol/L) between visits GCN and CHO	Continuous	0-180 min
Incidence of hyperglycemia (PG >10.0 mmol/L) between visits GCN and CHO	Binary	0-180 mins
Nadir PG concentration between visits GCN and CHO	Continuous	0-180 mins
Peak PG concentration between visits GCN and CHO	Continuous	0-180 mins
Incremental peak PG concentration between visits GCN and CHO	Continuous	0-180 mins
Mean PG concentration between visits GCN and CHO	Continuous	0-180 mins
PG area under the curve (AUC) between visits GCN and CHO	Continuous	0-180 mins
Standard deviation of PG between visits GCN and CHO	Continuous	0-180 mins
Coefficient of variation of PG between visits GCN and CHO	Continuous	0-180 mins

Collaborators and Investigators

• Sponsor: Steno Diabetes Center Copenhagen
• Investigators: Study Director: Kirsten Nørgaard, MD, Professor, Steno Diabetes Center Copenhagen

Study record dates

Study Major Dates

• Study Start (Estimated): March 15, 2026
• Primary Completion (Estimated): May 1, 2027
• Study Completion (Estimated): May 1, 2028

Study Registration Dates

• First Submitted: February 16, 2026
• First Submitted That Met QC Criteria: February 16, 2026
• First Posted (Actual): February 23, 2026

Study Record Updates

• Last Update Posted (Actual): February 27, 2026
• Last Update Submitted That Met QC Criteria: February 24, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Endocrine System Diseases; Metabolic Diseases; Autoimmune Diseases; Immune System Diseases; Glucose Metabolism Disorders; Diabetes Mellitus; Nutritional and Metabolic Diseases; Diabetes Mellitus, Type 1; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptide Hormones; Peptides; Amino Acids, Peptides, and Proteins; Pancreatic Hormones; Proglucagon; Glucagon
• Other Study ID Numbers: HypoAvoid_PostPrandial

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