Type2diabetesPhase 2NCT05499702
The Effects of Glucagon on Hepatic Metabolism in People With Type 2 Diabetes After Caloric Restriction
A Phase 2 study testing Caloric Restriction and Hyperglycemic clamp in people with Type2diabetes, run by Adrian Vella at 1 site in United States.
Trial summary
Caloric restriction (and RYGB) improves insulin action and lowers fasting glucose, glucagon and EGP, without changes in postprandial EGP and glucagon concentrations. Caloric restriction also improves hepatic steatosis and lowers fasting AA. These changes may represent restoration of glucagon's hepatic actions. Read more about this study
- Who is it for?
- Ages 25 to 65 years
- Conditions the study is for
- Type2diabetes
- What is being tested?
- Caloric Restriction and Hyperglycemic clamp
- Type of treatment
- Lifestyle or therapy programme
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteUnited States
- Study dates
- 15 Dec 2027to 31 Dec 2029
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
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
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- We will recruit up to 20 weight-stable, subjects with type 2 diabetes
- BMI ≥ 28 Kg/M2
- Diabetes is managed by diet alone or a combination of oral agents
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site
Mayo Clinic in Rochester
Rochester, Minnesota, 55905
About this study
Caloric restriction (and RYGB) improves insulin action and lowers fasting glucose, glucagon and EGP, without changes in postprandial EGP and glucagon concentrations. Caloric restriction also improves hepatic steatosis and lowers fasting AA. These changes may represent restoration of glucagon's hepatic actions. This experiment will determine whether caloric restriction improves glucagon's actions on hepatic amino acid, carbohydrate and lipid metabolism in T2DM in comparison to a baseline experiment performed separately in people with T2DM.
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 intact5. 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?
This study will determine how caloric restriction alters hepatic glucagon action. Elevated fasting AA concentrations are associated with T2DM risk. In addition, hepatic steatosis has been associated with an impaired ability of glucagon to stimulate hepatic clearance of AAs. Prior studies have shown that caloric restriction lowers fasting glucose, EGP and glucagon. However, the effects on these parameters in the postprandial period are unclear. This experiment will examine to what degree the improvements produced by caloric restriction can be explained by improved hepatic glucagon action. Because caloric restriction decreases hepatic fat content the experiment will also determine if a reduction in hepatic fat content is associated with changes in glucagon's effects on hepatic AA, glucose, and lipid metabolism.
- Conditions
- Type2diabetes
- Being tested
- Caloric Restriction, Hyperglycemic clamp
- Keywords
- glucagon, insulin resistance, caloric restriction, hepatic steatosis, amino acid metabolism
- Medical subject headings
- Insulin Resistance, Fatty Liver
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Caloric RestrictionBehavioural
Subjects will be instructed to consume a diet of 900 kcal daily using meals derived from "Nutritional Guidelines after Bariatric Surgery". Compliance will be monitored by weekly meetings with the dietician using an electronic record of food intake
Hyperglycemic clampDrug
Hyperglycemic clamp to measure the effect of glucagon on hepatic metabolism
| Study group | Role | What they receive |
|---|---|---|
| Adults with type 2 diabetes | Experimental | 20 subjects will be studied on one occasion, following 6 weeks of caloric restriction. They will be instructed to consume a diet of 900 kcal daily using meals derived from "Nutritional Guidelines after Bariatric Surgery". Compliance will be monitored by weekly meetings with the dietician using an electronic record of food intake. After this subjects will undergo a hyperglycemic clamp with 2 doses of glucagon infused. Receives: Behavioral: Caloric Restriction; Drug: Hyperglycemic clamp |
What is being measured
The primary outcome is the main question the study is designed to answer.
Rate of leucine oxidation in response to rising glucagon concentrations
tracer-determined amino acid catabolism
Measured: 240 minutes of study
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Aug 2022
- Study start15 Dec 2027 (estimated)
- Primary completion30 Jun 2029 (estimated)
- Study completion31 Dec 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Type2diabetesStudies 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 2
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- caloric restriction for six weeks
- Masking
- None (open label)
- Enrolment
- 20 participants (estimated)
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
- NCT05499702
- Sponsor's protocol ID
- 22-000233
- Status last verified
- Oct 2026
- First submitted
- 10 Aug 2022
- Last updated
- 28 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 28 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effects of Glucagon on Hepatic Metabolism in People With Type 2 Diabetes After Caloric Restriction
- ClinicalTrials.gov ID
- NCT05499702
- Acronym / sponsor ID
- 22-000233
- Conditions
- Type2diabetes
- Keywords
- glucagon, insulin resistance, caloric restriction, hepatic steatosis, amino acid metabolism
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 20 participants (estimated)
- Lead sponsor
- Adrian VellaUniversity, hospital or other
- Study start
- 15 Dec 2027 (estimated)
- Primary completion
- 30 Jun 2029 (estimated)
- Study completion
- 31 Dec 2029 (estimated)
- First posted
- 12 Aug 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Caloric restriction (and RYGB) improves insulin action and lowers fasting glucose, glucagon and EGP, without changes in postprandial EGP and glucagon concentrations. Caloric restriction also improves hepatic steatosis and lowers fasting AA. These changes may represent restoration of glucagon's hepatic actions. This experiment will determine whether caloric restriction improves glucagon's actions on hepatic amino acid, carbohydrate and lipid metabolism in T2DM in comparison to a baseline experiment performed separately in people with T2DM.
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 intact5. 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?
This study will determine how caloric restriction alters hepatic glucagon action. Elevated fasting AA concentrations are associated with T2DM risk. In addition, hepatic steatosis has been associated with an impaired ability of glucagon to stimulate hepatic clearance of AAs. Prior studies have shown that caloric restriction lowers fasting glucose, EGP and glucagon. However, the effects on these parameters in the postprandial period are unclear. This experiment will examine to what degree the improvements produced by caloric restriction can be explained by improved hepatic glucagon action. Because caloric restriction decreases hepatic fat content the experiment will also determine if a reduction in hepatic fat content is associated with changes in glucagon's effects on hepatic AA, glucose, and lipid metabolism.
Study design
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- caloric restriction for six weeks
| Arm | Type | Receives |
|---|---|---|
| Adults with type 2 diabetes | Experimental | Behavioral: Caloric Restriction, Drug: Hyperglycemic clamp20 subjects will be studied on one occasion, following 6 weeks of caloric restriction. They will be instructed to consume a diet of 900 kcal daily using meals derived from "Nutritional Guidelines after Bariatric Surgery". Compliance will be monitored by weekly meetings with the dietician using an electronic record of food intake. After this subjects will undergo a hyperglycemic clamp with 2 doses of glucagon infused. |
Who may qualify
- Ages
- 25 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- We will recruit up to 20 weight-stable, subjects with type 2 diabetes
- BMI ≥ 28 Kg/M2
- Diabetes is managed by diet alone or a combination of oral agents
Key exclusion criteria (7 listed)
- 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%
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Caloric RestrictionSubjects will be instructed to consume a diet of 900 kcal daily using meals derived from "Nutritional Guidelines after Bariatric Surgery". Compliance will be monitored by weekly meetings with the dietician using an electronic record of food intake | Behavioural | Adults with type 2 diabetes |
| Hyperglycemic clampHyperglycemic clamp to measure the effect of glucagon on hepatic metabolism | Drug | Adults with type 2 diabetes |
Primary outcome
Rate of leucine oxidation in response to rising glucagon concentrations
Time frame: 240 minutes of study
tracer-determined amino acid catabolism
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Oct 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Adrian Vella principal investigator
Mayo Clinic
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Caloric Restriction and Hyperglycemic clamp in people with Type2diabetes, run by Adrian Vella at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 28 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Jeanette Laugen (5072558110, Laugen.Jeanette@mayo.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Rate of leucine oxidation in response to rising glucagon concentrations (time frame: 240 minutes of study). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Oct 2026.