Understanding how genetics affect response to GLP1R agonists in obesity and diabetes

Pharmacogenetics of Response to GLP1R Agonists

PHASE1 · University of Maryland, Baltimore · NCT05071898

This study is testing how genetics affect the way overweight or obese people from the Old Order Amish community respond to the diabetes medication semaglutide.

Quick facts

PhasePHASE1
Study typeInterventional
Enrollment600 (estimated)
Ages18 Years to 89 Years
SexAll
SponsorUniversity of Maryland, Baltimore (other)
Locations1 site (Lancaster, Pennsylvania)
Trial IDNCT05071898 on ClinicalTrials.gov

What this trial studies

This study recruits overweight or obese volunteers from the Old Order Amish population in Lancaster County, PA, to investigate the pharmacogenetic responses to the GLP1R agonist semaglutide. Participants will undergo two frequently sampled intravenous glucose tolerance tests (FSIGT) before and after a six-week treatment with semaglutide. The study aims to identify genetic variants that influence insulin secretion and glucose disappearance rates in response to the medication. Genotyping will be performed using a high-density array to comprehensively analyze DNA sequence variants.

Who should consider this trial

Good fit: Ideal candidates are overweight or obese individuals of Amish descent with a BMI of 27 kg/m2 or higher.

Not a fit: Patients with a history of diabetes or those who are pregnant or planning to become pregnant may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could lead to personalized treatment strategies for obesity and type 2 diabetes based on genetic profiles.

How similar studies have performed: While pharmacogenetic approaches have been explored in other contexts, this specific investigation into GLP1R agonists in the Amish population is novel.

Eligibility criteria

Show full inclusion / exclusion criteria
Inclusion Criteria:

* BMI greater than or equal to 27 kg/m2
* Of Amish Descent

Exclusion Criteria:

* 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%
* 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

Where this trial is running

Lancaster, Pennsylvania

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.

View on ClinicalTrials.gov →

Conditions: Obesity, Diabetes Type 2, GLP-1 receptor agonist, Insulin secretion, Insulin sensitivity, Pharmacogenomics, Semaglutide

Last reviewed 2026-05-15 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.