PreDiabetesPhase 2NCT06967558
The Role of Islet GLP-1 in the Pathogenesis of Prediabetes
A Phase 2 study testing Exendin 9-39 and Saline in people with PreDiabetes, run by Mayo Clinic at 1 site in United States.
Trial summary
We recently demonstrated that blockade of Glucagon-Like Peptide-1's (GLP-1) receptor (GLP1R) results in changes in islet function without changes in circulating GLP-1. These effects are more pronounced in people with early type 2 diabetes (T2DM) in keeping with increased expression of PC-1/3 and GLP-1 that is observed… Read more about this study
- Who is it for?
- Ages 25 to 70 yearsHealthy volunteers can take part
- Conditions the study is for
- PreDiabetes
- What is being tested?
- Exendin 9-39 and Saline
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 60 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Nov 2025to 31 Mar 2028
- 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 70 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- People with stable weight and no history of diabetes.
- Fasting glucose < 126 mg/dL
- 2hr glucose after 75g OGTT < 200 mg/dL
Who cannot join
- Age < 25 or > 70 years (to avoid studying subjects who could have latent type 1 diabetes, or the effects of age extremes in subjects with normal or impaired fasting glucose).
- HbA1c > 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
Amy O'Byrne, 507-255-8547, OByrne.Amy14@mayo.edu
Adrian Vella
About this study
We recently demonstrated that blockade of Glucagon-Like Peptide-1's (GLP-1) receptor (GLP1R) results in changes in islet function without changes in circulating GLP-1. These effects are more pronounced in people with early type 2 diabetes (T2DM) in keeping with increased expression of PC-1/3 and GLP-1 that is observed in diabetic islets. However, its regulation is at present unknown. At present it is unknown if these abnormalities develop in prediabetes and whether they contribute to the phenotypes observed. In this experiment we will use blockade of GLP1R to probe the contribution of endogenous GLP-1 secretion to the regulation of fasting glucose and islet function in prediabetes.
Read the detailed description
We recently demonstrated that blockade of Glucagon-Like Peptide-1's (GLP-1) receptor (GLP1R) results in changes in islet function without changes in circulating GLP-1. This supports other evidence (rodents and humans) that through the (inducible) expression of a prohormone convertase (PC-1/3), the α-cell can process proglucagon to intact GLP-1. 'Islet' or 'pancreatic' GLP-1 acts in a paracrine fashion to regulate insulin and glucagon secretion. These effects are more pronounced in people with early type 2 diabetes (T2DM). Although pancreatic GLP-1 adapts to support islet function in T2DM, it is unclear if this mechanism is upregulated in prediabetes and whether it contributes to the phenotype(s) observed. Abnormal α-cell responsivity to glucose, measured using G50, is associated with Impaired Fasting Glucose (IFG); β-cell dysfunction is associated with Impaired Glucose Tolerance (IGT). Does IGT (or IFG) represent selective failure of intra-islet GLP-1 to support islet function? In this experiment we will use blockade of GLP1R to probe the contribution of endogenous GLP-1 secretion to the regulation of fasting glucose and islet function in prediabetes
- Conditions
- PreDiabetes
- Being tested
- Exendin 9-39, Saline
- Keywords
- Impaired Fasting Glucose, Impaired Glucose Tolerance, GLP-1
- Medical subject headings
- Prediabetic State, Glucose Intolerance
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Exendin 9-39Biological
Exendin 9-39 is a competitive antagonist of the GLP-1 receptor
SalineBiological
Saline
| Study group | Role | What they receive |
|---|---|---|
| Exendin 9-39 | Active comparator | Subjects will receive exendin 9-39 during the study Receives: Biological: Exendin 9-39 |
| Saline | Placebo comparator | Subjects will receive saline during the study Receives: Biological: Saline |
What is being measured
The primary outcome is the main question the study is designed to answer.
Alpha-cell responsivity to glucose as measured by G50
The change in glucose necessary to suppress glucagon secretion by 50%
Measured: 0-240 minutes
Beta-cell responsivity to glucose
This is measured as the gradient of the increase in insulin secretion rate per unit increase in glucose concentration
Measured: 0-240 minutes
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 May 2025
- Study start1 Nov 2025
- Primary completion30 Oct 2027 (estimated)
- Study completion31 Mar 2028 (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 2
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- we will study people with normal glucose tolerance with or without impaired fasting glucose together with people with impaired fasting glucose with or without impaired glucose tolerance. All subjects will be studied on 2 occasions - on one they will receive exendin 9-39 and on the other saline
- 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
- NCT06967558
- Sponsor's protocol ID
- 24-007677
- Status last verified
- Dec 2025
- First submitted
- 5 May 2025
- Last updated
- 15 Dec 2025
- 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 15 Dec 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Role of Islet GLP-1 in the Pathogenesis of Prediabetes
- ClinicalTrials.gov ID
- NCT06967558
- Acronym / sponsor ID
- 24-007677
- Conditions
- PreDiabetes
- Keywords
- Impaired Fasting Glucose, Impaired Glucose Tolerance, GLP-1
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 60 participants (estimated)
- Lead sponsor
- Mayo ClinicUniversity, hospital or other
- Study start
- 1 Nov 2025 (actual)
- Primary completion
- 30 Oct 2027 (estimated)
- Study completion
- 31 Mar 2028 (estimated)
- First posted
- 13 May 2025 (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.
We recently demonstrated that blockade of Glucagon-Like Peptide-1's (GLP-1) receptor (GLP1R) results in changes in islet function without changes in circulating GLP-1. These effects are more pronounced in people with early type 2 diabetes (T2DM) in keeping with increased expression of PC-1/3 and GLP-1 that is observed in diabetic islets. However, its regulation is at present unknown. At present it is unknown if these abnormalities develop in prediabetes and whether they contribute to the phenotypes observed. In this experiment we will use blockade of GLP1R to probe the contribution of endogenous GLP-1 secretion to the regulation of fasting glucose and islet function in prediabetes.
Detailed description
We recently demonstrated that blockade of Glucagon-Like Peptide-1's (GLP-1) receptor (GLP1R) results in changes in islet function without changes in circulating GLP-1. This supports other evidence (rodents and humans) that through the (inducible) expression of a prohormone convertase (PC-1/3), the α-cell can process proglucagon to intact GLP-1. 'Islet' or 'pancreatic' GLP-1 acts in a paracrine fashion to regulate insulin and glucagon secretion. These effects are more pronounced in people with early type 2 diabetes (T2DM). Although pancreatic GLP-1 adapts to support islet function in T2DM, it is unclear if this mechanism is upregulated in prediabetes and whether it contributes to the phenotype(s) observed. Abnormal α-cell responsivity to glucose, measured using G50, is associated with Impaired Fasting Glucose (IFG); β-cell dysfunction is associated with Impaired Glucose Tolerance (IGT). Does IGT (or IFG) represent selective failure of intra-islet GLP-1 to support islet function? In this experiment we will use blockade of GLP1R to probe the contribution of endogenous GLP-1 secretion to the regulation of fasting glucose and islet function in prediabetes
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- we will study people with normal glucose tolerance with or without impaired fasting glucose together with people with impaired fasting glucose with or without impaired glucose tolerance. All subjects will be studied on 2 occasions - on one they will receive exendin 9-39 and on the other saline
| Arm | Type | Receives |
|---|---|---|
| Exendin 9-39 | Active comparator | Biological: Exendin 9-39Subjects will receive exendin 9-39 during the study |
| Saline | Placebo comparator | Biological: SalineSubjects will receive saline during the study |
Who may qualify
- Ages
- 25 to 70 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- People with stable weight and no history of diabetes.
- Fasting glucose < 126 mg/dL
- 2hr glucose after 75g OGTT < 200 mg/dL
Key exclusion criteria (7 listed)
- Age < 25 or > 70 years (to avoid studying subjects who could have latent type 1 diabetes, or the effects of age extremes in subjects with normal or impaired fasting glucose).
- HbA1c > 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.
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 |
|---|---|---|
| Exendin 9-39Exendin 9-39 is a competitive antagonist of the GLP-1 receptor | Biological | Exendin 9-39 |
| SalineSaline | Biological | Saline |
Primary outcome
Alpha-cell responsivity to glucose as measured by G50
Time frame: 0-240 minutes
The change in glucose necessary to suppress glucagon secretion by 50%
Beta-cell responsivity to glucose
Time frame: 0-240 minutes
This is measured as the gradient of the increase in insulin secretion rate per unit increase in glucose concentration
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 15 Dec 2025.
- 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, 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 Phase 2 study testing Exendin 9-39 and Saline 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 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: looking for participants now, as of the sponsor's last update on 15 Dec 2025. 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.
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 Adrian Vella, MD (507-255-6515, vella.adrian@mayo.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Alpha-cell responsivity to glucose as measured by G50 (time frame: 0-240 minutes). The study lists 2 primary outcomes in all. 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 15 Dec 2025.