Pharmacogenetics of Response to GLP1R Agonists

NCT05071898 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: HP00097563
• Study Type: interventional
• Target: 600
• Locations: 1 country
• Sites: 1

Brief 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 for six weeks. The proposal proposes two specific aims:

1. 1.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).
2. 2.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).

Conditions

Obesity; Diabetes Type 2

Keywords

GLP-1 receptor agonist; Insulin secretion; Insulin sensitivity; Pharmacogenomics; Semaglutide

Outcome Measures

Primary Outcomes (3)

• 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 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 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 both at baseline and after completing 6 weeks of semaglutide therapy

Secondary Outcomes (1)

• Weight loss

  Assessed after completing 6 weeks of semaglutide therapy

Other Outcomes (2)

• Insulin sensitivity (Si)

  Measured both at baseline and after completing 6 weeks of semaglutide therapy

• Glucose effectiveness (Sg)

  Measured both at baseline and after completing 6 weeks of semaglutide therapy

Study Arms (1)

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

Drug: Semaglutide Pen Injector [Ozempic]

Interventions

Semaglutide Pen Injector [Ozempic] DRUG

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.

Also known as: Ozempic, Wegovy

Open label administration of semaglutide

Eligibility Criteria

• Age: 18 Years - 89 Years
• Gender Eligibility Details: Individuals will self-identify as being male, female, or other non-binary gender identity. Although we anticipate that most Amish will self-identify as being either male or female, everyone is potentially eligible regardless of their gender identity.
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Maryland, Baltimore: lead

Study Sites (1)

Amish Research Clinic

Lancaster, Pennsylvania, 17602, United States

RECRUITING

Related Publications (1)

• 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.

  PMID: 37264484 DERIVED

MeSH Terms

Conditions

Obesity; Diabetes Mellitus, Type 2; Insulin Resistance

Interventions

semaglutide

Condition Hierarchy (Ancestors)

Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Hyperinsulinism

Study Officials

• Amber L Beitelshees, PharmD

  University of Maryland, Baltimore

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Amber L Beitelshees, PharmD

CONTACT

(410)706-0118; abeitels@som.umaryland.edu

Simeon I Taylor, MD, PhD

CONTACT

(410)706-6439; staylor2@som.umaryland.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Medicine

Model Details: The study will employ a paired design with each participant being studied both before and after receiving semaglutide treatment for six weeks.

Study Record Dates

• First Submitted: September 27, 2021
• First Posted: October 8, 2021
• Study Start: April 11, 2022
• Primary Completion (Estimated): November 30, 2026
• Study Completion (Estimated): December 31, 2027
• Last Updated: July 1, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Two years after PIs have published the results of the clinical trial
• Access Criteria: Academic researchers who sign data sharing agreement to protect the confidentiality of the participants.

Locations

US (1)