Type 2 DiabetesPhase 1NCT05762744

Pharmacogenomics of GLP1 Receptor Agonists

A Phase 1 study testing Exenatide Injection (before the first FSIGT) and Exenatide injection before the second FSIGT) in people with Type 2 Diabetes, run by University of Maryland, Baltimore at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record

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Trial summary

Who is it for?: Ages 18 years and olderHealthy volunteers can take part
Conditions the study is for: Type 2 Diabetes
What is being tested?: Exenatide Injection (before the first FSIGT) and Exenatide injection before the second FSIGT)
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 63 participants
Where: 1 siteUnited States
Study dates: 1 Jun 2016to 31 Oct 2022
Phase: Phase 1
Are there results?: Yes, posted in the registrySummary in the doctors' view

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 18 years and older
All sexes
Healthy volunteers accepted
Adult, Older adult

Who may be able to join

Member of the Old Order Amish community in Lancaster County, Pennsylvania
BMI: 18-40 kg/sq.m.

Who cannot join

Known allergy to exenatide
History of diabetes, random glucose >200 mg/dL, or HbA1c > 6.5%
Significant debilitating chronic cardiac, hepatic, pulmonary, or renal disease or other diseases that the investigator judges will make interpretation of the results difficult or increase the risk of participation
Seizure disorder
Pregnant by self-report or known pregnancy within 3 months of the start of study
Currently breast feeding or breast feeding within 3 months of the start of the study

Show all 11Show fewer

Estimated glomerular filtration rate <60 mL/min/1.73m2
Hematocrit <35%
Liver function tests greater than 2 times the upper limit of normal
Abnormal thyroid stimulating hormone
History of pancreatitis or pancreatic cancer. Personal or family history of medullary carcinoma of the thyroid.

Trial locations and contacts

1 site in 1 country.

United States1 site

Amish Research Clinic
Lancaster, Pennsylvania, 17602

Other trials in United States

About this study

Healthy volunteers were recruited from the Old Order Amish population in Lancaster County, Pennsylvania. After providing informed consent, research participants were screened for eligibility. The clinical trial was designed as a randomized crossover study in which participants underwent two frequently sampled intravenous glucose tolerance tests - one after receiving a subcutaneous injection of saline and one after receiving a subcutaneous injection of rapid-acting exenatide (BYETTA). The study sought to determine whether genetic variants are associated with the magnitude of the effect of exenatide. However, because the study fell far short of its recruitment targets, it was under-powered to evaluate genetic association. Thus, the data analysis focused on testing the hypothesis that the order of testing (whether the placebo FSIGT was conducted before the exenatide-stimulated FSIGT or whether the FSIGTs were conducted in the reverse order) does not alter the magnitude impact of exenatide on responses to a frequently sampled iv glucose tolerance test.

Read the detailed description

Healthy volunteers were recruited from the Old Order Amish population in Lancaster County, Pennsylvania. After providing informed consent, research participants were screened for eligibility. The clinical trial was designed as a randomized crossover study in which participants underwent two frequently sampled intravenous glucose tolerance tests (FSIGT) - one after receiving a subcutaneous injection of saline and one after receiving a subcutaneous injection of rapid-acting exenatide (BYETTA). Based on data obtained from the FSIGT, participants' response to exenatide was assessed -- specifically, the effect of exenatide to enhance insulin secretion and accelerate metabolism of glucose. The study sought to determine whether genetic variants are associated with the magnitude of the effect of exenatide. However, because the study fell far short of its recruitment targets, it was under-powered to evaluate genetic association. Thus, the data analysis focused on testing the hypothesis that the order of testing (whether the placebo FSIGT was conducted before the exenatide-stimulated FSIGT or whether the FSIGTs were conducted in the reverse order) does not alter the magnitude impact of exenatide on responses to a frequently sampled iv glucose tolerance test.

Conditions: Type 2 Diabetes
Being tested: Exenatide Injection (before the first FSIGT), Exenatide injection before the second FSIGT)
Keywords: GLP1, insulin, glucose, exenatide, GLP1 receptor agonist, insulin secretion, glucagon receptor, GIP receptor
Medical subject headings: Diabetes Mellitus, Type 2, Insulin Resistance

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Exenatide Injection (before the first FSIGT)Drug
Also called BYETTA, Exenatide
Nurses administered exenatide (5 mcg) subcutaneously 15 minutes prior to conducting the first frequently sampled intravenous glucose tolerance test.
In this crossover study, participants will also be "crossed over" to receive saline rather than exenatide: Nurses administered saline (0.2 mL) subcutaneously 15 minutes prior to conducting a frequently sampled intravenous glucose tolerance test.
Exenatide injection before the second FSIGT)Drug
Also called BYETTA, Exenatide
Nurses administered exenatide (5 mcg) subcutaneously 15 minutes prior to conducting the second frequently sampled intravenous glucose tolerance test.

Study groups in NCT05762744
Study group	Role	What they receive
Exenatide followed by saline	Other	Participants were randomized to receive exenatide 15 min before the first frequently sampled iv glucose tolerance test and saline 15 min before the second frequently sampled iv glucose tolerance test Receives: Drug: Exenatide Injection (before the first FSIGT)
Saline followed by exenatide	Other	Participants were randomized to receive saline15 min before the first frequently sampled iv glucose tolerance test and exenatide15 min before the second frequently sampled iv glucose tolerance test Receives: Drug: Exenatide injection before the second FSIGT)

What is being measured

The primary outcome is the main question the study is designed to answer.

Exenatide Effect on First Phase Insulin Secretion
The ratio of the area-under-the-curve (AUC) for 1st phase insulin secretion in the exenatide-stimulated FSIGT divided by the AUC for 1st phase insulin secretion in the saline FSIGT.
Measured: 0-10 minutes
Exenatide Effect on Glucose Disappearance Rate
The ratio of the glucose disappearance rate (exenatide) divided by the glucose disappearance rate (placebo).
Glucose disappearance rates were calculated as the slope of the plot of the logarithm of the glucose concentration as a function of time.
Measured: 25-50 minutes

Secondary outcomes (6)

Glucose Disappearance Rate (Exenatide)
The slope of the line plotting the logarithm of glucose concentrations as a function of time during the exenatide frequently sampled intravenous glucose tolerance test. The slope of the line was estimated as the slope of the least-squares fit to the data points between 25-50 minutes.
Measured: 25-50 minutes
Glucose Disappearance Rate (Placebo)
The slope of the line plotting the logarithm of glucose concentrations as a function of time during the placebo frequently sampled intravenous glucose tolerance test. The slope of the line was estimated as the slope of the least-squares fit to the data points between 25-50 minutes.
Measured: 25-50 minutes
First Phase Insulin Secretion (Exenatide)
The area under the curve for plasma insulin levels during a frequently sampled intravenous glucose tolerance test after participants received exenatide
Measured: 0-10 minutes
First Phase Insulin Secretion (Placebo)
The area under the curve for plasma insulin levels during a frequently sampled intravenous glucose tolerance test after participants received saline
Measured: 0-10 minutes
Drug Effect on First-Phase Insulin Secretion (Genotype-specific)
The effect of exenatide to increase first-phase insulin secretion was defined as the ratio of area-under-the-curve (AUC) for insulin levels during the first 10 minutes of the exenatide-stimulated FSIGT divided by the AUC for first phase insulin secretion during the saline FSIGT..
Measured: 0 - 10 min during the FSIGT
Exenatide's Effect on the Rate of Glucose-disappearance (Genotype Specific)
The rate of glucose disappearance was calculated as the slope of a least-squared line fitted to the logarithms of glucose concentrations during time 25-50 min of FSIGTs
Measured: 25-50 min during the FSIGT

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

1 Jun 201631 Oct 2022

First posted10 Mar 2023
Study start1 Jun 2016
Primary completion30 Nov 2018
Study completion31 Oct 2022

Why it stopped: We concluded that it would not be possible to meet our recruitment targets within the available budget. The study was ended when the funding ended.

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.
Publications (2)Papers the sponsor has linked to this study.
Other trials for Type 2 DiabetesStudies of the same condition, open and under way.
More trials run by University of Maryland, BaltimoreThe 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 1
Primary purpose: Basic science
Allocation: Randomised
Intervention model: Crossover
Model description: Research participants all received the same two interventions (saline or exenatide) but the order of the interventions was randomized.
Masking: Single blind
Who is masked: Participant
Enrolment: 63 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT05762744
Sponsor's protocol ID: HP-00067574
Status last verified: Jun 2025
First submitted: 23 Feb 2023
Last updated: 1 Jul 2025
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: Yes: Subject to protection of confidential information of research participants, we will share data with qualified researchers.

Publications

Taylor SI, Montasser ME, Yuen AH, Fan H, Yazdi ZS, Whitlatch HB, Mitchell BD, Shuldiner AR, Muniyappa R, Streeten EA, Beitelshees AL. Acute pharmacodynamic responses to exenatide: Drug-induced increases in insulin secretion and glucose effectiveness. Diabetes Obes Metab. 2023 Sep;25(9):2586-2594. doi: 10.1111/dom.15143. Epub 2023 Jun 1.
PubMed 37264484
Beitelshees AL, Streeten EA, Shahidzadeh Yazdi Z, Whitlatch HB, Mitchell BD, Shuldiner AR, Montasser ME, Taylor SI. Acute pharmacodynamic responses to sitagliptin: Drug-induced increase in early insulin secretion in oral glucose tolerance test. Clin Transl Sci. 2024 May;17(5):e13809. doi: 10.1111/cts.13809.
PubMed 38700326

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 1 Jul 2025. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Pharmacogenomics of GLP1 Receptor Agonists
ClinicalTrials.gov ID: NCT05762744
Acronym / sponsor ID: HP-00067574
Conditions: Type 2 Diabetes
Keywords: GLP1, insulin, glucose, exenatide, GLP1 receptor agonist, insulin secretion, glucagon receptor, GIP receptor
Phase: Phase 1
Study type: Interventional
Recruitment status: TerminatedReason stopped: We concluded that it would not be possible to meet our recruitment targets within the available budget. The study was ended when the funding ended.
Enrolment: 63 participants (actual)
Lead sponsor: University of Maryland, BaltimoreUniversity, hospital or other
Study start: 1 Jun 2016 (actual)
Primary completion: 30 Nov 2018 (actual)
Study completion: 31 Oct 2022 (actual)
First posted: 10 Mar 2023 (actual)
Results: Posted 1 Jul 2025

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Healthy volunteers were recruited from the Old Order Amish population in Lancaster County, Pennsylvania. After providing informed consent, research participants were screened for eligibility. The clinical trial was designed as a randomized crossover study in which participants underwent two frequently sampled intravenous glucose tolerance tests (FSIGT) - one after receiving a subcutaneous injection of saline and one after receiving a subcutaneous injection of rapid-acting exenatide (BYETTA). Based on data obtained from the FSIGT, participants' response to exenatide was assessed -- specifically, the effect of exenatide to enhance insulin secretion and accelerate metabolism of glucose. The study sought to determine whether genetic variants are associated with the magnitude of the effect of exenatide. However, because the study fell far short of its recruitment targets, it was under-powered to evaluate genetic association. Thus, the data analysis focused on testing the hypothesis that the order of testing (whether the placebo FSIGT was conducted before the exenatide-stimulated FSIGT or whether the FSIGTs were conducted in the reverse order) does not alter the magnitude impact of exenatide on responses to a frequently sampled iv glucose tolerance test.

Study design

Primary purpose: Basic science
Allocation: Randomised
Intervention model: Crossover
Masking: Single blind (participant)
Number of arms: 2
Model description: Research participants all received the same two interventions (saline or exenatide) but the order of the interventions was randomized.

Arm	Type	Receives
Exenatide followed by saline	Other	Drug: Exenatide Injection (before the first FSIGT)Participants were randomized to receive exenatide 15 min before the first frequently sampled iv glucose tolerance test and saline 15 min before the second frequently sampled iv glucose tolerance test
Saline followed by exenatide	Other	Drug: Exenatide injection before the second FSIGT)Participants were randomized to receive saline15 min before the first frequently sampled iv glucose tolerance test and exenatide15 min before the second frequently sampled iv glucose tolerance test

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Accepted
Age groups: Adult, Older adult

Key inclusion criteria (2 listed)

Member of the Old Order Amish community in Lancaster County, Pennsylvania
BMI: 18-40 kg/sq.m.

Key exclusion criteria (11 listed)

Known allergy to exenatide
History of diabetes, random glucose >200 mg/dL, or HbA1c > 6.5%
Significant debilitating chronic cardiac, hepatic, pulmonary, or renal disease or other diseases that the investigator judges will make interpretation of the results difficult or increase the risk of participation
Seizure disorder
Pregnant by self-report or known pregnancy within 3 months of the start of study

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
Exenatide Injection (before the first FSIGT)Also: BYETTA, ExenatideNurses administered exenatide (5 mcg) subcutaneously 15 minutes prior to conducting the first frequently sampled intravenous glucose tolerance test. In this crossover study, participants will also be "crossed over" to receive saline rather than exenatide: Nurses administered saline (0.2 mL) subcutaneously 15 minutes prior to conducting a frequently sampled intravenous glucose tolerance test.	Drug	Exenatide followed by saline
Exenatide injection before the second FSIGT)Also: BYETTA, ExenatideNurses administered exenatide (5 mcg) subcutaneously 15 minutes prior to conducting the second frequently sampled intravenous glucose tolerance test.	Drug	Saline followed by exenatide

Primary outcome

Exenatide Effect on First Phase Insulin Secretion
Time frame: 0-10 minutes
The ratio of the area-under-the-curve (AUC) for 1st phase insulin secretion in the exenatide-stimulated FSIGT divided by the AUC for 1st phase insulin secretion in the saline FSIGT.
Exenatide Effect on Glucose Disappearance Rate
Time frame: 25-50 minutes
The ratio of the glucose disappearance rate (exenatide) divided by the glucose disappearance rate (placebo). Glucose disappearance rates were calculated as the slope of the plot of the logarithm of the glucose concentration as a function of time.

6 secondary outcomes

Glucose Disappearance Rate (Exenatide)
Time frame: 25-50 minutes
Glucose Disappearance Rate (Placebo)
Time frame: 25-50 minutes
First Phase Insulin Secretion (Exenatide)
Time frame: 0-10 minutes
First Phase Insulin Secretion (Placebo)
Time frame: 0-10 minutes
Drug Effect on First-Phase Insulin Secretion (Genotype-specific)
Time frame: 0 - 10 min during the FSIGT
Exenatide's Effect on the Rate of Glucose-disappearance (Genotype Specific)
Time frame: 25-50 min during the FSIGT

Results and safety

Results posted to the registry on 1 Jul 2025, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Exenatide Followed by Normal Saline	31	26
Normal Saline Followed by Exenatide	32	26

Primary outcome: Exenatide Effect on First Phase Insulin Secretion

Time frame: 0-10 minutes. Mean (Standard Error). Unit: Ratio (no units)

Measure	Exenatide First Followed by Saline n = 26	Saline First Followed by Exenatide n = 26
Value	1.90 (0.17)	2.18 (0.25)

Exenatide First Followed by Saline vs Saline First Followed by Exenatide: p = 0.37, t-test, 2 sided

Population analysed: The analysis population included 52 patients who completed the study and for whom the necessary blood samples were collected and available for assays of insulin and glucose.

Primary outcome: Exenatide Effect on Glucose Disappearance Rate

Time frame: 25-50 minutes. Mean (Standard Error). Unit: Ratio (no units)

Measure	Exenatide First Followed by Saline n = 26	Saline First Followed by Exenatide n = 26
Value	2.16 (0.19)	2.28 (0.20)

Exenatide First Followed by Saline: p = 0.66, t-test, 2 sided

Population analysed: The analysis population included 52 patients who completed the study and for whom the necessary blood samples were collected and available for assays of insulin and glucose.

6 secondary outcomes are reported in the full results.

Adverse events

Time frame: Adverse events were assessed during the time (one day) participants were in the clinic for the frequently sampled intravenous glucose tolerance test. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Total Study Population (Control Study)	0 of 62 (0%)	3 of 62 (4.8%)	0 of 62
Total Study Population (Exenatide Study)	0 of 62 (0%)	7 of 62 (11.3%)	0 of 62

Limitations and caveats (from the sponsor): The study was terminated before achieving the recruitment targets of 24 participants for each genotype group. Thus, the study was under-powered. The data analysis tested the null hypothesis that the order in which participants received exenatide or normal saline does not affect the response to a frequently sampled intravenous glucose tolerance test. The database is too small to permit meaningful analysis of the incidence of relatively minor adverse events (headaches, nausea, and vomiting).

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 1 Jul 2025.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Background: PubMed 37264484Taylor SI, Montasser ME, Yuen AH, Fan H, Yazdi ZS, Whitlatch HB, Mitchell BD, Shuldiner AR, Muniyappa R, Streeten EA, Beitelshees AL. Acute pharmacodynamic responses to exenatide: Drug-induced increases in insulin secretion and glucose effectiveness. Diabetes Obes Metab. 2023 Sep;25(9):2586-2594. doi: 10.1111/dom.15143. Epub 2023 Jun 1.
Derived from this study: PubMed 38700326Beitelshees AL, Streeten EA, Shahidzadeh Yazdi Z, Whitlatch HB, Mitchell BD, Shuldiner AR, Montasser ME, Taylor SI. Acute pharmacodynamic responses to sitagliptin: Drug-induced increase in early insulin secretion in oral glucose tolerance test. Clin Transl Sci. 2024 May;17(5):e13809. doi: 10.1111/cts.13809.
Individual participant dataSharing planned: Yes. Subject to protection of confidential information of research participants, we will share data with qualified researchers.

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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. This study is not recruiting at the moment.

Simeon I Taylor, MD principal investigator

University of Maryland, Baltimore

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

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 2 inclusion and 11 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: stopped early, as of the sponsor's last update on 1 Jul 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. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 1 Jul 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Exenatide Effect on First Phase Insulin Secretion (time frame: 0-10 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?

On the ClinicalTrials.gov record for NCT05762744, which also lists 2 linked publications.

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 1 Jul 2025.