PreDiabetesNCT06424106
Effect of Glucagon on Fasting Insulin Secretion and Glucose Metabolism in Subjects Without Type 2 Diabetes
A study testing Glucagon and Glucose in people with PreDiabetes, run by Mayo Clinic at 1 site in United States.
Trial summary
Fasting hyperglycemia contributes disproportionately to nonenzymatic glycosylation and the microvascular complications of type 2 diabetes. However, little is known about the regulation of glucose concentrations in the fasting state relative to what is known about the postprandial state. Read more about this study
- Who is it for?
- Ages 25 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- PreDiabetes
- What is being tested?
- Glucagon and Glucose
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 60 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Apr 2025to 1 Jul 2027
- Phase
- Interventional
- 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
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Individuals with normal or impaired fasting glucose and normal or impaired glucose tolerance
Who cannot join
- HbA1c less than 6.5%
- Use of any glucose-lowering agents including metformin or sulfonylureas.
- 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.
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, 1 recruiting
- Recruiting
Mayo Clinic in Rochester
Rochester, Minnesota, 55905
About this study
Fasting hyperglycemia contributes disproportionately to nonenzymatic glycosylation and the microvascular complications of type 2 diabetes. However, little is known about the regulation of glucose concentrations in the fasting state relative to what is known about the postprandial state. The proposed experiment is part of a series of experiments designed to establish how glucagon and insulin interact with their receptors to control fasting glucose in health and in prediabetes.
Read the detailed description
The interaction between α-cell and β-cell function to regulate fasting glucose is incompletely understood. This is an important gap in our knowledge as fasting glucose contributes disproportionately to HbA1c and the microvascular complications of type 2 diabetes (T2DM). The regulation of fasting glucose in health and disease is relatively understudied.
Insulin and glucagon should regulate glucose reciprocally through direct interaction; insulin restrains α-cell secretion while glucagon directly stimulates β-cell secretion. In addition, there are indirect interactions via changes in glucose. Glucagon increases endogenous glucose production (EGP) increasing glucose (and insulin secretion). Conversely, insulin stimulates glucose disappearance (Rd) and suppresses EGP, lowering glucose (and stimulating glucagon).
However, this does not appear to occur uniformly in prediabetes. For example, in impaired fasting glucose (IFG), glucagon secretion rate (GSR) is inappropriate for the prevailing glucose. This is not accompanied by reciprocal changes in insulin secretion rate (ISR). Variability in the hepatic response to glucagon and to insulin further compound the dysregulation of fasting glucose. The net effect of these variables is unknown. This experiment is intended to test the hypothesis that impaired glucagon-induced insulin secretion contributes to fasting hyperglycemia in IFG.
- Conditions
- PreDiabetes
- Being tested
- Glucagon, Glucose
- Keywords
- Insulin secretion, glucagon secretion, endogenous glucose production, glucose disappearance
- Medical subject headings
- Prediabetic State
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GlucagonOther
a variable rate glucagon infusion
GlucoseOther
a variable rate glucose infusion
| Study group | Role | What they receive |
|---|---|---|
| Glucagon Infusion | Active comparator | A glucagon infusion (0.2 ng/kg/min) will start at 0900 (0 min), increasing to 0.4 (1000), 0.6 (1100) and 0.8 ng/kg/min (1200) at 60-minute intervals - ending at 1300 (240 min). Receives: Other: Glucagon |
| Glucose Infusion | Placebo comparator | At 0900 (0 min) a glucose infusion will commence, and the infusion rate varied to replicate (± 5mg/dL) that individual's glucose concentrations observed during the Glucagon Infusion Day. The experiment will end at 1300 (240 min) when infusions are stopped. Receives: Other: Glucose |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in beta-cell responsivity induced by glucagon
The beta-cell responsivity observed during glucagon infusion will be compared to that observed during glucose infusion
Measured: Beta-cell responsivity will be calculated as the gradient of the relationship between glucose concentrations and insulin secretion rate during the study day over the 4 hours (0 to 240 minutes) of the study
Secondary outcomes (2)
change in endogenous glucose production induced by glucagon
The endogenous glucose production observed during glucagon infusion will be compared to that observed during glucose infusion
Measured: The rate of endogenous glucose production at the end of the study (240 minutes) will be expressed as a percentage of that at the beginning of the study (0 minutes). The % change for each study day will then be compared
change in glucose disappearance induced by glucagon
The glucose disappearance observed during glucagon infusion will be compared to that observed during glucose infusion
Measured: The rate of glucose disappearance at the end of the study (240 minutes) will be expressed as a percentage of that at the beginning of the study (0 minutes). The % change for each study day will then be compared
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 May 2024
- Study start1 Apr 2025
- Primary completion1 Jul 2027 (estimated)
- Study completion1 Jul 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for PreDiabetesStudies of the same condition, open and under way.
- More trials run by Mayo ClinicThe sponsor's other registered studies.
- 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 N/A
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Model description
- All participants will complete two experiments conducted in random order. On one day they will receive a graded glucagon infusion while on the other they will receive a glucose infusion that replicates the glucose concentrations observed in the first study day
- Masking
- None (open label)
- Enrolment
- 60 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Mayo Clinic
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Adrian Vella, Mayo Clinic
- Investigators
- Adrian Vella, MD, Principal investigator, Mayo Clinic
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06424106
- Sponsor's protocol ID
- 24-002639
- Status last verified
- Apr 2026
- First submitted
- 13 May 2024
- Last updated
- 20 Apr 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: In addition to the patient-level data, the metadata, data dictionary, statistical analysis plan, and final protocol will be shared. The sharing of the data dictionary, statistical analysis plan and final protocol with amendments will enable researchers to understand how the data was collected and to correctly interpret the data for future secondary analysis. We plan to share datasets resulting from the proposed studies in Vivli, a non-profit institution that supports the Vivli repository.
Study at a glance
From the registry record, last updated by the sponsor on 20 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Glucagon on Fasting Insulin Secretion and Glucose Metabolism in Subjects Without Type 2 Diabetes
- ClinicalTrials.gov ID
- NCT06424106
- Acronym / sponsor ID
- 24-002639
- Conditions
- PreDiabetes
- Keywords
- Insulin secretion, glucagon secretion, endogenous glucose production, glucose disappearance
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 60 participants (estimated)
- Lead sponsor
- Mayo ClinicUniversity, hospital or other
- Study start
- 1 Apr 2025 (actual)
- Primary completion
- 1 Jul 2027 (estimated)
- Study completion
- 1 Jul 2027 (estimated)
- First posted
- 21 May 2024 (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.
Fasting hyperglycemia contributes disproportionately to nonenzymatic glycosylation and the microvascular complications of type 2 diabetes. However, little is known about the regulation of glucose concentrations in the fasting state relative to what is known about the postprandial state. The proposed experiment is part of a series of experiments designed to establish how glucagon and insulin interact with their receptors to control fasting glucose in health and in prediabetes.
Detailed description
The interaction between α-cell and β-cell function to regulate fasting glucose is incompletely understood. This is an important gap in our knowledge as fasting glucose contributes disproportionately to HbA1c and the microvascular complications of type 2 diabetes (T2DM). The regulation of fasting glucose in health and disease is relatively understudied.
Insulin and glucagon should regulate glucose reciprocally through direct interaction; insulin restrains α-cell secretion while glucagon directly stimulates β-cell secretion. In addition, there are indirect interactions via changes in glucose. Glucagon increases endogenous glucose production (EGP) increasing glucose (and insulin secretion). Conversely, insulin stimulates glucose disappearance (Rd) and suppresses EGP, lowering glucose (and stimulating glucagon).
However, this does not appear to occur uniformly in prediabetes. For example, in impaired fasting glucose (IFG), glucagon secretion rate (GSR) is inappropriate for the prevailing glucose. This is not accompanied by reciprocal changes in insulin secretion rate (ISR). Variability in the hepatic response to glucagon and to insulin further compound the dysregulation of fasting glucose. The net effect of these variables is unknown. This experiment is intended to test the hypothesis that impaired glucagon-induced insulin secretion contributes to fasting hyperglycemia in IFG.
Study design
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- All participants will complete two experiments conducted in random order. On one day they will receive a graded glucagon infusion while on the other they will receive a glucose infusion that replicates the glucose concentrations observed in the first study day
| Arm | Type | Receives |
|---|---|---|
| Glucagon Infusion | Active comparator | Other: GlucagonA glucagon infusion (0.2 ng/kg/min) will start at 0900 (0 min), increasing to 0.4 (1000), 0.6 (1100) and 0.8 ng/kg/min (1200) at 60-minute intervals - ending at 1300 (240 min). |
| Glucose Infusion | Placebo comparator | Other: GlucoseAt 0900 (0 min) a glucose infusion will commence, and the infusion rate varied to replicate (± 5mg/dL) that individual's glucose concentrations observed during the Glucagon Infusion Day. The experiment will end at 1300 (240 min) when infusions are stopped. |
Who may qualify
- Ages
- 25 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- Individuals with normal or impaired fasting glucose and normal or impaired glucose tolerance
Key exclusion criteria (6 listed)
- HbA1c less than 6.5%
- Use of any glucose-lowering agents including metformin or sulfonylureas.
- 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.
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 |
|---|---|---|
| Glucagona variable rate glucagon infusion | Other | Glucagon Infusion |
| Glucosea variable rate glucose infusion | Other | Glucose Infusion |
Primary outcome
Change in beta-cell responsivity induced by glucagon
Time frame: Beta-cell responsivity will be calculated as the gradient of the relationship between glucose concentrations and insulin secretion rate during the study day over the 4 hours (0 to 240 minutes) of the study
The beta-cell responsivity observed during glucagon infusion will be compared to that observed during glucose infusion
2 secondary outcomes
change in endogenous glucose production induced by glucagon
Time frame: The rate of endogenous glucose production at the end of the study (240 minutes) will be expressed as a percentage of that at the beginning of the study (0 minutes). The % change for each study day will then be compared
change in glucose disappearance induced by glucagon
Time frame: The rate of glucose disappearance at the end of the study (240 minutes) will be expressed as a percentage of that at the beginning of the study (0 minutes). The % change for each study day will then be compared
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 20 Apr 2026.
- Individual participant dataSharing planned: Yes. In addition to the patient-level data, the metadata, data dictionary, statistical analysis plan, and final protocol will be shared. The sharing of the data dictionary, statistical analysis plan and final protocol with amendments will enable researchers to understand how the data was collected and to correctly interpret the data for future secondary analysis. We plan to share datasets resulting from the proposed studies in Vivli, a non-profit institution that supports the Vivli repository.
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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, MD 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 study testing Glucagon and Glucose in people with PreDiabetes, run by Mayo Clinic 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 1 inclusion and 6 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: looking for participants now, as of the sponsor's last update on 20 Apr 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. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
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 Kim Osmundson, CCRP (507-255-0907, Osmundson.Kimberly@mayo.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in beta-cell responsivity induced by glucagon (time frame: Beta-cell responsivity will be calculated as the gradient of the relationship between glucose concentrations and insulin secretion rate during the study day over the 4 hours (0 to 240 minutes) of the 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 20 Apr 2026.