The Separate and Combined Glucagonotropic Effects of Glucose-dependent Insulinotropic Polypeptide and Alanine in Subjects With and Without Type 1 Diabetes

NCT06881472 | Completed

• 1 other identifier: H-21066812-113790
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

The hormone glucose-dependent insulinotropic polypeptide (GIP) is naturally produced in the intestine during a meal and stimulates insulin secretion from the pancreas. Insulin ensures that nutrients from the meal are transported from the blood into the cells, allowing the body to use it as energy. If blood sugar levels drop too much, the body naturally releases another hormone: glucagon. Glucagon is responsible for the breakdown of nutrients inside the cells, thus causing blood sugar levels to rise again. This occurs, for example, when a person is fasting or in an energy deficit. Unfortunately, glucagon is not released in people with type 1 diabetes when blood sugar levels are low. However, it is known that GIP contributes to the secretion of glucagon during low blood sugar levels in both healthy individuals and those with type 1 diabetes. Protein intake through the diet is broken down in the body into amino acids. It is known that the ingestion of protein and thus amino acids leads to an increase in glucagon in both healthy individuals and those with type 1 diabetes. This causes the amino acids to be converted into sugar, but also allows potentially harmful waste products from the breakdown to be converted into harmless components. The relationship between GIP and amino acids, as well as their joint effect on glucagon, is still unknown, but studies in mice have shown that if GIP and amino acids are given simultaneously, glucagon secretion will be even higher than if they were administered separately. The purpose of this study is to gain a better understanding of how the three (GIP, amino acids, and glucagon) are interconnected and affect each other and to see if the experiments conducted in mice yield the same results in healthy individuals and those with type 1 diabetes. Moreover, the secretion of glucagon, and thus the increase in blood sugar, might protect individuals with type 1 diabetes from experiencing low blood sugar. This knowledge could potentially be used for new treatment approaches in diabetes in the future.

Conditions

Type 1 Diabetes

Keywords

GIP; Amino acids; Alanine

Outcome Measures

Primary Outcomes (1)

• bsAUC of glucagon concentration

  Baseline Area under the curve of Glucagon concentration

  From 0-150 minutes

Secondary Outcomes (2)

• bsAUC Glucagon 30-90

  from 30-90 minutes

• bsAUC glucagon 90-150 min

  from 90-150 minutes

Study Arms (4)

GIP

ACTIVE COMPARATOR

Drug: Glucose-dependent Insulinotropic Polypeptide (GIP); Drug: Saline (NaCl 0,9 %) (placebo)

Alanine

ACTIVE COMPARATOR

Drug: alanine; Drug: Saline (NaCl 0,9 %) (placebo)

GIP + Alanine

ACTIVE COMPARATOR

Drug: Glucose-dependent Insulinotropic Polypeptide (GIP); Drug: alanine

Placebo

PLACEBO COMPARATOR

Drug: Saline (NaCl 0,9 %) (placebo)

Interventions

alanine DRUG

Alanine

Alanine; GIP + Alanine

Glucose-dependent Insulinotropic Polypeptide (GIP) DRUG

GIP

GIP; GIP + Alanine

Saline (NaCl 0,9 %) (placebo) DRUG

Placebo

Alanine; GIP; Placebo

Eligibility Criteria

• Age: 18 Years - 70 Years
• Gender Eligibility Details: Only biological males, only cisgender men.
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 20-27 kg/m2
• T1D duration of 2-20 years
• C-peptide negative (arginin-stimulated C-peptide ≤ 100 pmol/l)
• Treatment with a stable basal-bolus or insulin pump regimen for ≥3 months
• Informed and written consent

You may not qualify if:

• Anaemia (haemoglobin below normal range)
• Late microvascular complications except mild nonproliferative retinopathy
• Liver disease (alanine aminotransferase (ALAT) and/or aspartate aminotransferase (ASAT) \>2 times normal values) or history of hepatobiliary disorder
• Treatment with any glucose-lowering drugs beside insulin
• Active or recent (within 5 years) malignant disease
• Active tobacco smoking / use
• Any condition considered incompatible with participation by the investigators

Sponsors & Collaborators

• Asger Lund, MD: lead

Study Sites (1)

Gentofte Hospital

Hellerup, 2900, Denmark

Location

MeSH Terms

Conditions

Diabetes Mellitus, Type 1

Interventions

Incretins; Alanine; Sodium Chloride

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs; Pharmacologic Actions; Chemical Actions and Uses; Amino Acids; Amino Acids, Peptides, and Proteins; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate professor, MD, Ph.D.

Study Record Dates

• First Submitted: March 11, 2025
• First Posted: March 18, 2025
• Study Start: January 1, 2025
• Primary Completion: January 16, 2026
• Study Completion: January 16, 2026
• Last Updated: April 29, 2026

Record last verified: 2026-04

Locations

DK (1)