Glucagon Resistance in Patients With MASLD and T2DM

February 3, 2026 updated by: University of Aarhus

Mechanisms for Glucagon Resistance as Driver of Metabolic Associated Steatotic Liver Disease and Cardiovascular Disease in Humans With Type 2 Diabetes

The goal of this clinical trial is to investigate the sensitivity to glucagon in patients with type 2 diabetes mellitus (T2DM), with and without metabolic associated fatty liver disease (MASLD).

The main questions it aims to answer are:

  1. Is the sensitivity to glucagon with respect to hepatic FA oxidation and suppression of VLDL-TG secretion impaired in humans with T2DM and MASLD?
  2. Is glucagon resistance and MASLD reflected in an aberrated lipidomic/metabolomic profile in blood and adipose tissue?

Researchers will compare patients with T2DM with and without MASLD to see if the response to basal and high levels of glucagon differs between the groups.

Participants will attend 2 short visits and 1 full-day visit, including:

  • Body scan (DXA) to check fat and bone composition
  • MRI to measure liver fat.
  • Blood tests.
  • Ultrasound to check liver stiffness and scarring.
  • Fat biopsies
  • 8-hour hormone (including glucagon) and tracer infusion
  • PET-CT scans

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

24

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Denmark
      • Aarhus, Denmark, 8000
        • Recruiting
        • Aarhus University Hospital
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • BMI > 26 kg/m²
  • confirmed diagnosis of Type 2 Diabetes Mellitus (T2DM) min. 6 months prior enrollment
  • steatosis FF% > 5,6% on MR spectroscopy for MAFLD group

Exclusion Criteria:

  • Alcohol abuse (>10 units per week for both sexes) or other substance abuse
  • Smoking
  • Current or previous malignant disease
  • Blood donation within the last 3 months prior to the study day
  • Participation in studies involving radioactive isotopes within the past 3 months
  • Pregnancy
  • Severely dysregulated type 2 diabetes mellitus (haemoglobin A1c ≥ 100 mmol/mol)
  • C-peptide < 200 pmol/L
  • Previous acute myocardial infarction (AMI)
  • Clinical symptoms of heart failure
  • Current or previous malignant disease
  • Known ongoing systemic disease, except for dyslipidaemia and hypertension

  • Regular use of medication that may affect lipid and glucose metabolism, including insulin treatment, regular use of over-the-counter medications, and hormonal contraception. Exceptions:

    1. Participants treated with statins may be included following a 2-week washout period prior to the experimental study day.
    2. Participants receiving oral glucose-lowering therapy for T2DM and antihypertensive medication may be included provided that medication is withheld on the study day only.
    3. Participants receiving weekly injectable glucagon-like peptide-1 receptor agonists (GLP-1 analogues) may be included following a 1-week washout period prior to the study day.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Subjects with T2DM and MR spectroscopy verified NO steatosis
Other: Glugagon

Infusion of low dose glucagon and high dose glucagon during simultaneous somatostatin infusion and replacement doses of insulin and growth hormone. Infusion of palmitate, VLDL-triglyceride and glucose tracers.

[11C]palmitate PET during low and high dose glucagon.
Active Comparator: Subjects with T2DM and MR spectroscopy verified steatosis
Other: Glugagon

Infusion of low dose glucagon and high dose glucagon during simultaneous somatostatin infusion and replacement doses of insulin and growth hormone. Infusion of palmitate, VLDL-triglyceride and glucose tracers.

[11C]palmitate PET during low and high dose glucagon.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Hepatic FFA oxidation rate (µmol/100Ml/min)
Time Frame: 30 minutes at steady-state
Measured using [11C]palmitate positron-emission tomography (PET)
30 minutes at steady-state
Blood and adipose tissue proteomic and lipidomic profiles
Time Frame: 30 minutes after steady-state
Mass spectrometry-based lipidomic/proteomic profiles of paired adipose and plasma samples.
30 minutes after steady-state

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
VLDL-triglyceride kinetics (appearance rate (µmol/min) and oxidation (µmol/min))
Time Frame: 30 minutes at steady-state
Ex vivo labeled VLDL [14C]-triolein tracer technique. Oxidation is measured by specific activity in exhaled air.
30 minutes at steady-state
Endogen glucose production (mmol/kg/min)
Time Frame: 30 minutes at steady-state
3-3H glucose tracer technique
30 minutes at steady-state
Fatty acid turnover (µmol/min)
Time Frame: 30 minutesat steady-state
Infusion af [9,10-3H] palmitate and measurement of specific activity
30 minutesat steady-state

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Aarhus

Collaborators

Novo Nordisk A/S

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 29, 2026

Primary Completion (Estimated)

July 31, 2027

Study Completion (Estimated)

July 31, 2028

Study Registration Dates

First Submitted

November 17, 2025

First Submitted That Met QC Criteria

November 17, 2025

First Posted (Actual)

November 24, 2025

Study Record Updates

Last Update Posted (Actual)

February 4, 2026

Last Update Submitted That Met QC Criteria

February 3, 2026

Last Verified

December 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • MASLD_GLUCA2025
  • 0092321 (Other Grant/Funding Number: Steno Collaborative Grant, Novo Nordisk Foundation)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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