Pharmacogenetics of Response to Sitagliptin (PRS) (PRS)

Sitagliptin's Effects on Glucose-stimulated Insulin Secretion and Oral Glucose

This is a research study to find out how different people respond to a medication called sitagliptin. Sitagliptin is an FDA approved medication that is used to treat diabetes. We are asking for healthy, non-diabetic volunteers to participate in this 7-week study. If you agree to participate, you will take part in 2 clinic visits that are 4-6 weeks apart. At the clinic visits you will have an oral glucose tolerance test (OGTT) and other blood tests to see how your body processes glucose (sugar). An OGTT is a test in which your drink glucose and then blood samples are taken afterward at specific time points to measure glucose and insulin in your blood. Each clinic visit will last about 5 hours.

Study Overview

• Status: Not yet recruiting
• Conditions: Diabetes
• Intervention / Treatment: Procedure: Oral Glucose Tolerance Test

• Study Type: Interventional
• Enrollment (Estimated): 400
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Amber L Beitelshees; Phone Number: 14107060118; Email: abeitels@som.umaryland.edu
• Study Contact Backup: Name: Kamah Woelfel; Email: KWoelfel@som.umaryland.edu

Study Locations

• United States
  • Pennsylvania
    • Lancaster, Pennsylvania, United States, 17602
      • University of Maryland Amish Research Clinic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• • Age: >18 years old

  • Members of Old Order Amish community in Lancaster, PA

Exclusion Criteria:

• • Pregnancy (reproductive age women will undergo pregnancy tests immediately before receiving the drug)

  • Diabetes: HbA1c > 6.5% or fasting plasma glucose >126 mg/dL
  • Estimated glomerular filtration rates (eGFR) <60 mL/min/1.73 m2
  • Anemia: hematocrit < 35%
  • Thyroid status: TSH<0.4 or TSH>5.5
  • ALT or AST in excess of 2X upper limit of normal
  • Drugs that in the physician's judgment would alter response to sitagliptin
  • Significant health issues that in the physician's judgment could increase the risk for participants.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Sitagliptin; Sitagliptin 100 mg given 2 hours prior to the oral glucose tolerance test	Procedure: Oral Glucose Tolerance Test; Three hour glucose tolerance test
Placebo Comparator: Placebo; Placebo given 2 hours prior to the oral glucose tolerance test	Procedure: Oral Glucose Tolerance Test; Three hour glucose tolerance test

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Sitagliptin-induced enhancement of early insulin secretion	This represents the incretinomimetic effect of sitagliptin, which contributes importantly to the mechanism whereby DPP4is decrease HbA1c in T2D patients. Because histograms for sitagliptin-induced increase in our index of early insulin secretion (T30:T60) demonstrated a skewed distribution, we will apply a logarithmic transformation of data which yields a normal distribution. Thus, the drug effect is defined as: log(T30:T60 ins)sita - log(T30:T60 ins)control.	6 weeks
Sitagliptin-induced change in glucose tolerance	Sitagliptin-induced change in glucose tolerance. This is a consequence of enhanced insulin secretion, which reflects most closely the desired effect of the drug to decrease plasma glucose and decrease HbA1c. Because histograms for sitagliptin-induced increase in our index of glucose tolerance (T30:T60) demonstrated a skewed distribution, we will apply a logarithmic transformation of data which yields a normal distribution. Thus, the drug effect is defined as: log(T30:T60 gluc)sita - log(T30:T60 gluc)control.	6 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area under the curve for insulin concentration	Area under the curve of insulin concentration measured from oral glucose tolerance test using trapezoidal rule	6 weeks
Area under the curve for glucose concentration	Area under the curve for glucose concentration measured from the oral glucose tolerance test using the trapezoidal rule	6 weeks
Area under the curve for intact GIP	Area under the curve for levels of intact GIP during the first hour of the OGTT as calculated by the trapezoidal rule	6 weeks
Area under the curve for intact GLP1	Area under the curve for levels of intact GLP1 during the first hour of the OGTT as calculated by the trapezoidal rule	6 weeks
Area under the curve for C-peptide levels	Area under the curve for C-peptide levels as a direct index of insulin secretion	6 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Parameters of a mathematical model (insulin secretion and glucose sensitivity of the β-cell	We will apply mathematical modeling to the oral glucose tolerance test data it assess measures of insulin secretion and glucose sensitivity of the β-cell	6 weeks

Collaborators and Investigators

• Sponsor: University of Maryland, Baltimore
• Investigators: Principal Investigator: Amber L Beitelshees, PharmD, MPH, University of Maryland, Baltimore; Principal Investigator: Simeon I Taylor, MD, PhD, University of Maryland, Baltimore

Study record dates

Study Major Dates

• Study Start (Estimated): December 1, 2026
• Primary Completion (Estimated): November 1, 2031
• Study Completion (Estimated): December 1, 2032

Study Registration Dates

• First Submitted: February 3, 2025
• First Submitted That Met QC Criteria: February 3, 2025
• First Posted (Actual): February 6, 2025

Study Record Updates

• Last Update Posted (Actual): February 18, 2026
• Last Update Submitted That Met QC Criteria: February 17, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Endocrine System Diseases; Metabolic Diseases; Glucose Metabolism Disorders; Nutritional and Metabolic Diseases; Diabetes Mellitus; Investigative Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Blood Chemical Analysis; Clinical Chemistry Tests; Diagnostic Techniques, Endocrine; Glucose Tolerance Test
• Other Study ID Numbers: HP-00111892

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: Given that the Amish are a unique founder population, they are more easily identified and at-risk for stigmatization. Therefore, we must consult with the community in order to address this plan to share individual level data.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No