The Effects of Glucagon on Hepatic Metabolism

NCT05500586 | Completed Phase 1 FDA Drug

• 1 other identifier: 22-000113
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 1

Brief Summary

Whether impaired postprandial glucagon suppression in prediabetes and T2DM is an attempt to overcome resistance to glucagon's actions on hepatic AA catabolism, a defect in α-cell function, or a combination of both are important, unanswered questions. NAFLD is associated with T2DM risk and impaired insulin action. Unfortunately, it is unclear if glucagon resistance is caused by obesity, hepatic steatosis or both. The experiments outlined will determine if glucagon's actions on hepatic amino acid catabolism and EGP interact with hepatic lipid metabolism in lean and obese subjects with and without T2DM (and with varying degrees of hepatic steatosis).

Conditions

Obesity; Type2diabetes; NAFLD

Keywords

glucagon; insulin resistance; hepatic steatosis; amino acid metabolism

Outcome Measures

Primary Outcomes (1)

• Rate of Amino acid catabolism in the presence / absence of glucagon

  Tracer-dependent measurement of amino-acid clearance

  240 minutes of study

Secondary Outcomes (1)

• Effect of Diabetes on amino-acid catabolism

  240 minutes of study

Study Arms (3)

Healthy Adults

EXPERIMENTAL

We will study 20 subjects on one occasion using a hyperglycemic clamp with 2 doses of glucagon.

Drug: Glucagon response study

Obese Adults

EXPERIMENTAL

We will study 20 subjects on one occasion using a hyperglycemic clamp with 2 doses of glucagon.

Drug: Glucagon response study

Adults with Type 2 Diabetes

EXPERIMENTAL

We will study 20 subjects on one occasion using a hyperglycemic clamp with 2 doses of glucagon.

Drug: Glucagon response study

Interventions

Glucagon response study DRUG

Please see information in group descriptions

Also known as: Glucagon

Adults with Type 2 Diabetes; Healthy Adults; Obese Adults

Eligibility Criteria

• Age: 25 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Willing to participate
• Able to give consent

You may not qualify if:

• History of prior upper abdominal surgery e.g. gastric banding, pyloroplasty, vagotomy.
• Active systemic illness or malignancy.
• Symptomatic macrovascular or microvascular disease.
• Contraindications to MRI (e.g. metal implants, claustrophobia).
• Hematocrit \< 35%
• TSH \< 0.4 or \> 5.5.
• Consumption of \> 2 alcohol drinks per day or \> 14 per week or a positive AUDIT questionnaire

Sponsors & Collaborators

• Adrian Vella: lead

Study Sites (1)

Mayo Clinic in Rochester

Rochester, Minnesota, 55905, United States

Location

Related Links

• Mayo Clinic Clinical Trials

MeSH Terms

Conditions

Obesity; Non-alcoholic Fatty Liver Disease; Insulin Resistance; Fatty Liver

Interventions

Glucagon

Condition Hierarchy (Ancestors)

Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Liver Diseases; Digestive System Diseases; Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases

Intervention Hierarchy (Ancestors)

Proglucagon; Pancreatic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptides; Amino Acids, Peptides, and Proteins

Study Officials

• Adrian Vella

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Regulatory Sponsor

Model Details: All subjects will undergo one study designed to measure the hepatic response to glucagon. There will be 3 groups non-diabetic and non-obese, obese, people with type 2 diabetes

Study Record Dates

• First Submitted: August 10, 2022
• First Posted: August 15, 2022
• Study Start: October 20, 2022
• Primary Completion: September 30, 2025
• Study Completion: March 31, 2026
• Last Updated: April 29, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)