ObesityPhase 1/2NCT05500586
The Effects of Glucagon on Hepatic Metabolism
A Phase 1/2 study testing Glucagon response study in people with Obesity and Type2diabetes, run by Adrian Vella at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 25 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Obesity, Type2diabetes, NAFLD
- What is being tested?
- Glucagon response study
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 21 participants
- Where
- 1 siteUnited States
- Study dates
- 20 Oct 2022to 31 Mar 2026
- Phase
- Phase 1/2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 25 to 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Type 2 diabetes
- BMI ≥ 28 Kg/M2
- Managed by diet alone or a combination of metformin and/or sulfonylurea
- Willing to stop glucose-lowering medication for 3 weeks prior to participation and willing to self-monitor their fasting glucose during this time
- No history of micro- or macrovascular complications of T2DM
- -Subjects who do not have type 2 diabetes but are age and sex but are not weight-matched (BMI ≤ 25 Kg/M2) with subjects who have T2DM
Who cannot join
- Age < 25 or > 65 years
- HbA1c ≥ 8.5%
- BMI ≤ 28 Kg/M2
- For female subjects: positive pregnancy test at the time of enrollment or study
- History of prior upper abdominal surgery such as adjustable gastric banding, pyloroplasty and vagotomy.
- Active systemic illness or malignancy.
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- Symptomatic macrovascular or microvascular disease.
- Known contraindications to MRI
- Hematocrit < 35%
- History of uncontrolled thyroid disease
- Consumption of > 2 alcohol drinks per day or > 14 per week or a positive AUDIT questionnaire.
- Allergy to iodine
- Thrombocytopenia, history of bleeding disorder or use of anticoagulation
- Subjects with treatment change or significant weight change (≥ 10%) in the prior 3 months.
- Inclusion Criteria - Obese subjects without Type 2 Diabetes:
- -Obese subjects without type 2 diabetes but are age, sex and weight-matched (BMI ≥ 28 Kg/M2) with subjects who have T2DM
- Exclusion Criteria - Obese Subjects without Type 2 Diabetes:
- Age < 25 or > 65 years (match subjects with T2DM)
- HbA1c ≥ 6.5%
- BMI ≤ 28 Kg/M2
- Use of any glucose-lowering agents
- For female subjects: positive pregnancy test at the time of enrollment or study
- History of prior upper abdominal surgery such as adjustable gastric banding, pyloroplasty and vagotomy.
- Active systemic illness or malignancy.
- Symptomatic macrovascular or microvascular disease.
- Known contraindications to MRI
- Hematocrit < 35%
- History of uncontrolled thyroid disease.
- Consumption of > 2 alcohol drinks per day or > 14 per week or a positive AUDIT questionnaire.
- Allergy to iodine
- Thrombocytopenia, history of bleeding disorder or use of anticoagulation
- Age < 25 or > 65 years (match subjects with T2DM)
- HbA1c ≥ 6.5%
- BMI ≥ 25 Kg/M2 unless % body fat is < 20% in males and < 30% in females.
- Use of any glucose-lowering agents
- For female subjects: positive pregnancy test at the time of enrollment or study
- History of prior upper abdominal surgery such as adjustable gastric banding, pyloroplasty and vagotomy.
- Active systemic illness or malignancy.
- Symptomatic macrovascular or microvascular disease.
- Known contraindications to MRI
- Hematocrit < 35%
- History of uncontrolled thyroid disease.
- Consumption of > 2 alcohol drinks per day or > 14 per week or a positive AUDIT questionnaire.
- Liver fat content ≥ 5% as determined by MRI using the proton density fat fraction (PDFF) technique.
- Allergy to iodine
- Thrombocytopenia, history of bleeding disorder or use of anticoagulation
Trial locations and contacts
1 site in 1 country.
United States1 site
Mayo Clinic in Rochester
Rochester, Minnesota, 55905
About this study
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).
Read the detailed description
T2DM and prediabetes are characterized by abnormal post-prandial suppression of glucagon, which contributes to postprandial hyperglycemia by increasing EGP. Although these effects are magnified by decreased and delayed insulin secretion, they are also apparent when insulin secretion is intact. In rodents, altered glucagon signaling changes α-cell function and mass - an effect mediated by changes in circulating AA concentrations. Are the elevated concentrations of branched-chain AA and other AA metabolites in T2DM a cause or an effect of global α-cell dysfunction? Could altered glucagon signaling precipitate a vicious cycle resulting in T2DM?
- Conditions
- Obesity, Type2diabetes, NAFLD
- Being tested
- Glucagon response study
- Keywords
- glucagon, insulin resistance, hepatic steatosis, amino acid metabolism
- Medical subject headings
- Obesity, Non-alcoholic Fatty Liver Disease, Insulin Resistance, Fatty Liver
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Glucagon response studyDrug
Also called Glucagon
Please see information in group descriptions
| Study group | Role | What they receive |
|---|---|---|
| Healthy Adults | Experimental | We will study 20 subjects on one occasion using a hyperglycemic clamp with 2 doses of glucagon. Receives: Drug: Glucagon response study |
| Obese Adults Protein Density Fat Fraction (PDFF) < 5% | Experimental | We will study 20 subjects on one occasion using a hyperglycemic clamp with 2 doses of glucagon. Receives: Drug: Glucagon response study |
| Adults with Type 2 Diabetes Protein Density Fat Fraction (PDFF) < 5% | Experimental | We will study 20 subjects on one occasion using a hyperglycemic clamp with 2 doses of glucagon. Receives: Drug: Glucagon response study |
| Adults with Type 2 Diabetes Protein Density Fat Fraction (PDFF) > 5% | Experimental | We will study 20 subjects on one occasion using a hyperglycemic clamp with 2 doses of glucagon. Receives: Drug: Glucagon response study |
| Obese Adults Protein Density Fat Fraction (PDFF) > 5% | Experimental | We will study 20 subjects on one occasion using a hyperglycemic clamp with 2 doses of glucagon. Receives: Drug: Glucagon response study |
What is being measured
The primary outcome is the main question the study is designed to answer.
Rate of Amino Acid Catabolism in the Presence / Absence of Glucagon
Amino acid catabolism assessed by leucine reamination, a surrogate measure of leucine oxidation, during fasting (0 minutes), intermediate glucagon infusion (120 minutes), and high glucagon infusion (240 minutes).
Measured: 0 minutes, 120 minutes, 240 minutes
Secondary outcomes (3)
Effect of Diabetes on Amino-acid Catabolism
Tracer-dependent measurement of amino-acid clearance
Measured: 240 minutes of study
Splanchnic Balance of Essential Amino Acids During Fasting and Glucagon Infusion
Splanchnic balance of essential amino acids calculated from the arteriovenous concentration difference across the liver multiplied by splanchnic blood flow. Measurements were obtained during fasting (0 minutes), intermediate glucagon infusion (120 minutes), and high glucagon infusion (240 minutes) to evaluate the effect of obesity and hepatic steatosis on glucagon-mediated amino acid metabolism.
Measured: 0 Minutes, 120 Minutes, 240 Minutes
Splanchnic Balance of Nonessential Amino Acids During Fasting and Glucagon Infusion
Splanchnic balance of nonessential amino acids calculated from the arteriovenous concentration difference across the liver multiplied by splanchnic blood flow. Measurements were obtained during fasting (0 minutes), intermediate glucagon infusion (120 minutes), and high glucagon infusion (240 minutes) to evaluate the effect of obesity and hepatic steatosis on glucagon-mediated amino acid metabolism.
Measured: 0 Minutes, 120 Minutes, 240 Minutes
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Aug 2022
- Study start20 Oct 2022
- Primary completion30 Sep 2025
- Study completion31 Mar 2026
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for ObesityStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Model description
- All subjects will undergo one study designed to measure the hepatic response to glucagon. There will be 5 groups non-diabetic and non-obese, obese PDFF \> 5%, obese PDFF \< 5% people with type 2 diabetes with PDFF \> 5%, people with type 2 diabetes with PDFF \< 5%.
- Masking
- None (open label)
- Enrolment
- 21 participants (actual)
Sponsor and investigators
- Lead sponsor
- Adrian Vella
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Adrian Vella, Mayo Clinic
- Investigators
- Adrian Vella, Principal investigator, Mayo Clinic
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05500586
- Sponsor's protocol ID
- 22-000113
- Other IDs
- R01DK116231
- Status last verified
- Sep 2026
- First submitted
- 10 Aug 2022
- Last updated
- 14 Oct 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No: No plan