The Effect of Endogenous GLP-1 on Glucagon Secretion in Type 1 Diabetes (EX-HYPO)

Examining the Effect of Endogenous Glucagon-like Peptide-1 on Glucagon Secretion in Type 1 Diabetes

Type 1 diabetes is a serious and burdensome disease that carries the risk of severe complications and premature death, partly due to low blood sugar, also called hypoglycaemia. This is a constant threat, as individuals with type 1 diabetes lack the body's natural safeguard against low blood sugar: the hormone glucagon, which is normally released from the pancreas.

Recent research in mice suggests that this missing safeguard may be due to an imbalance in the hormones released from different cells in the pancreas. More specifically, glucagon-like peptide-1 (GLP-1) appears to play a role in the lack of glucagon secretion. By blocking this hormone using the substance exendin(9-39)NH₂, normalization of glucagon release during low blood sugar has been observed in mice with type 1 diabetes.

The present study aims to investigate whether the same mechanism applies in humans with type 1 diabetes. If confirmed, this finding could form the basis for a novel adjunct treatment to insulin therapy and thereby potentially reduce the risk of hypoglycaemia in this patient group.

Study Overview

• Status: Completed
• Conditions: Type 1 Diabetes
• Intervention / Treatment: Drug: Saline (0.9% NaCl); Drug: exendin(9-39)amide

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Denmark
  • Hellerup, Denmark, 2100
    • Gentofte Hospital

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Caucasian ethnicity
• Age between 18 and 70 years
• T1D (diagnosed according to the criteria of the World Health Organization) with HbA1c <69 mmol/mol (<8.5%)
• Body mass index between 19 and 30 kg/m2
• T1D duration of 2-30 years
• C-peptide negative (5 gram arginine-stimulated C-peptide ≤100 pmol/l)
• Treatment with a stable basal-bolus or insulin pump regimen for ≥3 months

Exclusion Criteria:

• Anaemia (haemoglobin below normal range)
• Late microvascular complications except mild non-proliferative retinopathy
• Liver disease (Evaluated by alanine aminotransferase (ALAT) and/or aspartate aminotransferase (ASAT) >2 times normal values) or a history of hepatobiliary disorder
• Kidney disease (serum creatinine above normal range)
• Treatment with any glucose-lowering drugs beside insulin
• Active or recent (within 5 years) malignant disease
• Regular tobacco smoking or use of other nicotine-containing products
• Any condition considered incompatible with participation by the investigators.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Saline	Drug: Saline (0.9% NaCl); Placebo; Other Names: Placebo
Active Comparator: Exendin(9-39)NH2; GLP-1 antagonist	Drug: exendin(9-39)amide; GLP-1 antagonist

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
bsAUC Glucagon	Entire study periode	0-135 minutes

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
bsAUC of Glucagon	Primary endpoint	30-90 minutes
Total Glucose infused	Recovery phase glucose infused	90-135 minutes
Glucose infused (entire period)	Entire glucose infused	0-135 minutes
GLP-1	Circulating GLP-1	0-135 minutes
Cortisol	Cortisol	0-135 minutes

Collaborators and Investigators

• Sponsor: Asger Lund, MD

Study record dates

Study Major Dates

• Study Start (Actual): January 23, 2026
• Primary Completion (Actual): April 9, 2026
• Study Completion (Actual): April 9, 2026

Study Registration Dates

• First Submitted: November 20, 2025
• First Submitted That Met QC Criteria: January 22, 2026
• First Posted (Actual): January 28, 2026

Study Record Updates

• Last Update Posted (Actual): April 29, 2026
• Last Update Submitted That Met QC Criteria: April 28, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Hypoglycemia; GLP-1; Type 1 diabetes; Exendin(9-39)NH2
• Additional Relevant MeSH Terms: Endocrine System Diseases; Metabolic Diseases; Autoimmune Diseases; Immune System Diseases; Glucose Metabolism Disorders; Diabetes Mellitus; Nutritional and Metabolic Diseases; Hypoglycemia; Diabetes Mellitus, Type 1; Inorganic Chemicals; Chlorine Compounds; Sodium Compounds; Chlorides; Hydrochloric Acid; Sodium Chloride; exendin (9-39)
• Other Study ID Numbers: H-25032390

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