ObesityPhase 1PORTNCT05071898
Pharmacogenetics of Response to GLP1R Agonists
A Phase 1 study testing Semaglutide Pen Injector [Ozempic] in people with Obesity and Diabetes Type 2, run by University of Maryland, Baltimore at 1 site in United States.
Trial summary
Overweight/obese otherwise healthy volunteers will be recruited from the Old Order Amish population in Lancaster County, PA. Lancaster County, PA. Pharmacodynamic responses to GLP1R agonist will be assessed by conducting frequently sampled intravenous glucose tolerance tests (FSIGT) both before and after semaglutide… Read more about this study
- Who is it for?
- Ages 18 to 89 yearsHealthy volunteers can take part
- Conditions the study is for
- Obesity, Diabetes Type 2
- What is being tested?
- Semaglutide Pen Injector [Ozempic]
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 600 participants
- Where
- 1 siteUnited States
- Study dates
- 11 Apr 2022to Apr 2028
- Phase
- Phase 1
- 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 18 to 89 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- BMI greater than or equal to 27 kg/m2
- Of Amish Descent
Who cannot join
- Woman of childbearing age who is sexually active
- History of diabetes (HbA1c > 6.5% or random glucose >200 mg/dL)
- Known allergy to semaglutide
- Medical issues, which in the judgment of the research physician or PIs might increase the risk associated with participation in the study
- eGFR < 60 mL/min/1.73 sq. m.
- Hematocrit < 35%
Show all 10Show fewer
- TSH < 0.4 o4 > 5.5
- AST or ALT in excess of 2X the upper limit of normal
- Unable to discontinue a drug, vitamin, or nutritional supplement, which in the judgment of the research physician or PIs might alter the response to semaglutide
- Personal or family history of medullary carcinoma of the thyroid or multiple endocrine neoplasia, type 2
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
Amish Research Clinic
Lancaster, Pennsylvania, 17602
Susan Shaub, RN, (717)392-4948, sshaub@som.umaryland.edu
About this study
Overweight/obese otherwise healthy volunteers will be recruited from the Old Order Amish population in Lancaster County, PA. Lancaster County, PA. Pharmacodynamic responses to GLP1R agonist will be assessed by conducting frequently sampled intravenous glucose tolerance tests (FSIGT) both before and after semaglutide for six weeks. The proposal proposes two specific aims:
- Specific Aim #1. To identify genetic variants associated with effects of a GLP1R agonist to enhance glucose-stimulated first phase insulin secretion in the two FSIGTs (before and after administration of drug).
- Specific Aim #2. To identify genetic variants associated with the effect of a GLP1R agonist to accelerate the rate of glucose disappearance as assessed in the two FSIGTs (before and after administration of drug).
Genotyping will be conducted using a high-density array with comprehensive coverage of DNA sequence variants. In addition, the analysis will leverage a global imputation panel generated from 1,025 Amish individuals.
Read the detailed description
Overweight/obese otherwise healthy volunteers will be recruited from the Old Order Amish population in Lancaster County, PA. In order to assess pharmacodynamic responses, research participants will undergo two frequently sampled intravenous glucose tolerance tests (FSIGT). The first FSIGT will be conducted at baseline prior to administration of drug. The second FSIGT will be conducted after six weeks of treatment with semaglutide (0.25 mg/wk X 4 wks; 0.5 mg/sk X 2 wks). The proposal proposes two specific aims:
- Specific Aim #1. To identify genetic variants associated with effects of a GLP1R agonist to enhance glucose-stimulated first phase insulin secretion in the two FSIGTs (before and after administration of drug).
- Specific Aim #2. To identify genetic variants associated with the effect of a GLP1R agonist to accelerate the rate of glucose disappearance as assessed in the two FSIGTs (before and after administration of drug).
After being determined to be eligible and after having given informed consent, participants will undergo two frequently samples intravenous glucose tolerance tests conducted at two clinic visits as described below:
Visit #1 - Research participants will be transported to the Amish Research clinic in the fasting state (minimum of 8 hour, maximum of 24 hour fast) where height, weight, waist and hip measurements, and vital signs will be measured. Women of child-bearing potential will undergo a urine pregnancy test. An FSIVGTT will be conducted as follows: IV (intravenous) access will be established in both arms of the research participant, one for glucose infusion and the other for frequent blood sampling. NSS (normal saline solution) will be used to maintain patency of IV. Intravenous glucose (0.3 g/kg) will be infused over 2 min at time=0, and 31 blood samples will be obtained between -15 and +180 minutes. Approximately 180 ml (36 tsp.) of blood will be drawn. Upon completion of the FSIVGTT, the participant will be instructed in the self-administration of subcutaneous (s.c.) injection of semaglutide. The first dose of semaglutide .25mg will be administered at this time. The participant will be provided with a post-fasting meal.
Home self-administration of weekly semaglutide: The participant will self-administer s.c. semaglutide weekly for 5 weeks (.25 mg for weeks 2,3,4 and .5 mg for weeks 5,6) A research nurse may observe the participant self-administering the first home dose and will make additional home visits as needed to ensure successful self-injection. The participant will use the study provided scale to obtain and record daily weights in the morning before breakfast throughout the medication weeks.
Visit #2 - This visit will be scheduled within 1 week of the final (6th) dose of semaglutide +/- 5 days. The FSIVGTT will be conducted exactly as during the previous clinic visit.
Genotyping will be conducted using a high-density array with comprehensive coverage of DNA sequence variants. The project will leverage a global imputation panel generated from whole genome sequence data on ~ 100K subjects including 1,025 Amish individuals obtained through the NHLBI-sponsored Trans-Omics for Precision Medicine (TOPMed) program.
- Conditions
- Obesity, Diabetes Type 2
- Being tested
- Semaglutide Pen Injector [Ozempic]
- Keywords
- GLP-1 receptor agonist, Insulin secretion, Insulin sensitivity, Pharmacogenomics, Semaglutide
- Medical subject headings
- Obesity, 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.
Semaglutide Pen Injector [Ozempic]Drug
Also called Ozempic, Wegovy
Participants will receive subcutaneously injected semaglutide (0.25 mg/wk) for 4 weeks followed by semaglutide (0.5 mg/wk) for an additional two weeks.
| Study group | Role | What they receive |
|---|---|---|
| Open label administration of semaglutide | Experimental | Semaglutide: 0.25 mg, sc, q.week for 4 weeks followed by 0.5 mg, sc, q.week for 2 weeks Receives: Drug: Semaglutide Pen Injector [Ozempic] |
What is being measured
The primary outcome is the main question the study is designed to answer.
First phase insulin secretion
Area under the curve for plasma insulin levels measured at times between 0-10 min after administration of intravenous glucose (0.3 g/kg)
Measured: Measured both at baseline and after completing 6 weeks of semaglutide therapy
Second phase insulin secretion
Area under the curve for plasma insulin levels measured at times between 10-50 min after administration of intravenous glucose (0.3 g/kg)
Measured: Measured both at baseline and after completing 6 weeks of semaglutide therapy
Rate of glucose disappearance
Slope of the plot of log(glucose concentration) as a function of time. This will be calculated based on a linear regression using data points between 25-50 minutes after administration of intravenous glucose (0.3 g/kg)
Measured: Measured both at baseline and after completing 6 weeks of semaglutide therapy
Secondary outcomes (1)
Weight loss
This will be measured as the baseline weight in kg minus the weight after completing 6 weeks of semaglutide therapy.
Measured: Assessed after completing 6 weeks of semaglutide therapy
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Oct 2021
- Study start11 Apr 2022
- Primary completion30 Apr 2027 (estimated)
- Study completionApr 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for ObesityStudies 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
- Not applicable
- Intervention model
- Single group
- Model description
- The study will employ a paired design with each participant being studied both before and after receiving semaglutide treatment for six weeks.
- Masking
- None (open label)
- Enrolment
- 600 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Maryland, Baltimore
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Amber Beitelshees, University of Maryland, Baltimore
- Investigators
- Amber L Beitelshees, PharmD, Principal investigator, University of Maryland, Baltimore
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05071898
- Sponsor's protocol ID
- HP00097563
- Acronym
- PORT
- Status last verified
- Jul 2026
- First submitted
- 27 Sep 2021
- Last updated
- 27 Jul 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Within the constraints of assuring confidentiality of research participants, we plan to share deidentified IPD within two years after the study investigators have published the results of the research.
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
Study at a glance
From the registry record, last updated by the sponsor on 27 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pharmacogenetics of Response to GLP1R Agonists
- ClinicalTrials.gov ID
- NCT05071898
- Acronym / sponsor ID
- PORT / HP00097563
- Conditions
- Obesity, Diabetes Type 2
- Keywords
- GLP-1 receptor agonist, Insulin secretion, Insulin sensitivity, Pharmacogenomics, Semaglutide
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 600 participants (estimated)
- Lead sponsor
- University of Maryland, BaltimoreUniversity, hospital or other
- Study start
- 11 Apr 2022 (actual)
- Primary completion
- 30 Apr 2027 (estimated)
- Study completion
- Apr 2028 (estimated)
- First posted
- 8 Oct 2021 (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.
Overweight/obese otherwise healthy volunteers will be recruited from the Old Order Amish population in Lancaster County, PA. Lancaster County, PA. Pharmacodynamic responses to GLP1R agonist will be assessed by conducting frequently sampled intravenous glucose tolerance tests (FSIGT) both before and after semaglutide for six weeks. The proposal proposes two specific aims:
- Specific Aim #1. To identify genetic variants associated with effects of a GLP1R agonist to enhance glucose-stimulated first phase insulin secretion in the two FSIGTs (before and after administration of drug).
- Specific Aim #2. To identify genetic variants associated with the effect of a GLP1R agonist to accelerate the rate of glucose disappearance as assessed in the two FSIGTs (before and after administration of drug).
Genotyping will be conducted using a high-density array with comprehensive coverage of DNA sequence variants. In addition, the analysis will leverage a global imputation panel generated from 1,025 Amish individuals.
Detailed description
Overweight/obese otherwise healthy volunteers will be recruited from the Old Order Amish population in Lancaster County, PA. In order to assess pharmacodynamic responses, research participants will undergo two frequently sampled intravenous glucose tolerance tests (FSIGT). The first FSIGT will be conducted at baseline prior to administration of drug. The second FSIGT will be conducted after six weeks of treatment with semaglutide (0.25 mg/wk X 4 wks; 0.5 mg/sk X 2 wks). The proposal proposes two specific aims:
- Specific Aim #1. To identify genetic variants associated with effects of a GLP1R agonist to enhance glucose-stimulated first phase insulin secretion in the two FSIGTs (before and after administration of drug).
- Specific Aim #2. To identify genetic variants associated with the effect of a GLP1R agonist to accelerate the rate of glucose disappearance as assessed in the two FSIGTs (before and after administration of drug).
After being determined to be eligible and after having given informed consent, participants will undergo two frequently samples intravenous glucose tolerance tests conducted at two clinic visits as described below:
Visit #1 - Research participants will be transported to the Amish Research clinic in the fasting state (minimum of 8 hour, maximum of 24 hour fast) where height, weight, waist and hip measurements, and vital signs will be measured. Women of child-bearing potential will undergo a urine pregnancy test. An FSIVGTT will be conducted as follows: IV (intravenous) access will be established in both arms of the research participant, one for glucose infusion and the other for frequent blood sampling. NSS (normal saline solution) will be used to maintain patency of IV. Intravenous glucose (0.3 g/kg) will be infused over 2 min at time=0, and 31 blood samples will be obtained between -15 and +180 minutes. Approximately 180 ml (36 tsp.) of blood will be drawn. Upon completion of the FSIVGTT, the participant will be instructed in the self-administration of subcutaneous (s.c.) injection of semaglutide. The first dose of semaglutide .25mg will be administered at this time. The participant will be provided with a post-fasting meal.
Home self-administration of weekly semaglutide: The participant will self-administer s.c. semaglutide weekly for 5 weeks (.25 mg for weeks 2,3,4 and .5 mg for weeks 5,6) A research nurse may observe the participant self-administering the first home dose and will make additional home visits as needed to ensure successful self-injection. The participant will use the study provided scale to obtain and record daily weights in the morning before breakfast throughout the medication weeks.
Visit #2 - This visit will be scheduled within 1 week of the final (6th) dose of semaglutide +/- 5 days. The FSIVGTT will be conducted exactly as during the previous clinic visit.
Genotyping will be conducted using a high-density array with comprehensive coverage of DNA sequence variants. The project will leverage a global imputation panel generated from whole genome sequence data on ~ 100K subjects including 1,025 Amish individuals obtained through the NHLBI-sponsored Trans-Omics for Precision Medicine (TOPMed) program.
Study design
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- The study will employ a paired design with each participant being studied both before and after receiving semaglutide treatment for six weeks.
| Arm | Type | Receives |
|---|---|---|
| Open label administration of semaglutide | Experimental | Drug: Semaglutide Pen Injector [Ozempic]Semaglutide: 0.25 mg, sc, q.week for 4 weeks followed by 0.5 mg, sc, q.week for 2 weeks |
Who may qualify
- Ages
- 18 to 89 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- BMI greater than or equal to 27 kg/m2
- Of Amish Descent
Key exclusion criteria (10 listed)
- Woman of childbearing age who is sexually active
- History of diabetes (HbA1c > 6.5% or random glucose >200 mg/dL)
- Known allergy to semaglutide
- Medical issues, which in the judgment of the research physician or PIs might increase the risk associated with participation in the study
- eGFR < 60 mL/min/1.73 sq. m.
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 |
|---|---|---|
| Semaglutide Pen Injector [Ozempic]Also: Ozempic, WegovyParticipants will receive subcutaneously injected semaglutide (0.25 mg/wk) for 4 weeks followed by semaglutide (0.5 mg/wk) for an additional two weeks. | Drug | Open label administration of semaglutide |
Primary outcome
First phase insulin secretion
Time frame: Measured both at baseline and after completing 6 weeks of semaglutide therapy
Area under the curve for plasma insulin levels measured at times between 0-10 min after administration of intravenous glucose (0.3 g/kg)
Second phase insulin secretion
Time frame: Measured both at baseline and after completing 6 weeks of semaglutide therapy
Area under the curve for plasma insulin levels measured at times between 10-50 min after administration of intravenous glucose (0.3 g/kg)
Rate of glucose disappearance
Time frame: Measured both at baseline and after completing 6 weeks of semaglutide therapy
Slope of the plot of log(glucose concentration) as a function of time. This will be calculated based on a linear regression using data points between 25-50 minutes after administration of intravenous glucose (0.3 g/kg)
1 secondary outcome
Weight loss
Time frame: Assessed after completing 6 weeks of semaglutide therapy
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 27 Jul 2026.
- Derived from this study: 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.
- Individual participant dataSharing planned: Yes. Within the constraints of assuring confidentiality of research participants, we plan to share deidentified IPD within two years after the study investigators have published the results of the research.
Related trials for Obesity
RecruitingObservational study
Endoscopic Sleeve Gastroplasty (ESG) Prospective Trial for Obesity (EGO-Trial)
Obesity
Active, not recruitingPhase 4
Effects of Sequential Therapy With Mexidol® (Intravenous) and Mexidol® FORTE 250 (Oral) on Functional Brain Activity Assessed by Functional Magnetic Resonance Imaging and Biochemical Parameters in Patients With Chronic Cerebral Ischemia: A Comparison of Patients With and Without Metabolic Disorders
Metabolic Abnormalities, Obesity & Overweight
Recruiting
Exercise Training and Vitamin D Metabolism
Obesity & Overweight, Vitamin D
Recruiting
Metabolic Health, Bones and Nuts During Weight Loss in Adults
Weight Loss, Bone Density
Active, not recruiting
Effect of Probiotics on Insulin Sensitivity in Overweight and Obese Pregnancy
Obesity & Overweight, Gestational Diabetes Mellitus (GDM)
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.
Amber L Beitelshees, PharmD 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?
A Phase 1 study testing Semaglutide Pen Injector [Ozempic] in people with Obesity and Diabetes Type 2, run by University of Maryland, Baltimore 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 2 inclusion and 10 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 27 Jul 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 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?
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 Amber L Beitelshees, PharmD ((410)706-0118, abeitels@som.umaryland.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
First phase insulin secretion (time frame: Measured both at baseline and after completing 6 weeks of semaglutide therapy). The study lists 3 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 NCT05071898, which also lists 1 linked publication.
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 27 Jul 2026.