Effects of Sitagliptin in Individuals With Genetically Decreased DPP4

January 15, 2026 updated by: Jessica R.Wilson, MD, MS, University of Pennsylvania
This is a pilot clinical trial to test the hypothesis that during sitagliptin (DPP4 inhibitor), individuals heterozygous for DPP4 loss of function variants will have a reduction in DPP4 activity and antigen, lower glucose after a mixed meal, and higher levels of intact DPP4 substrates compared to during placebo and compared to matched controls.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Detailed Description

Participants of this pilot clinical trial will be randomized in a blinded 2:2 crossover manner to receive placebo and sitagliptin 100 mg/d (DPP4 inhibitor), in random order. Subjects will receive each intervention for seven days, with a study day on day 7. Each intervention will be separated by a 4-week washout period. Each subject will have up to four separate visits: 1) DXA, echocardiogram, 2) cardiac MRI, 3) mixed meal during placebo, 4) mixed meal during sitagliptin.

The study will include 10 cases (heterozygous for DPP4 loss of function variant) and 10 controls.

Study Type

Interventional

Enrollment (Estimated)

20

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
        • University of Pennsylvania

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 80 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Participant of the Penn Medicine Biobank who is willing to be recontacted to participate in future research.
  • Cases are defined as adults 18-70 years with likely decreased DPP4.
  • Controls are defined as adults who are matched to cases by: age, gender, race, BMI, hypertension status, diabetes status, renal function, and medication use that may affect outcomes of interest.

Exclusion Criteria:

  • The study will exclude volunteers with any significant medical conditions that may interfere with study participation, data interpretation, or pose safety risk(s) to the subject.
  • Recent hospitalization or acute illness such as infection within the past two weeks
  • Pregnancy
  • Use of insulin
  • Use of a GLP-1 agonist or DPP4 inhibitor medication
  • Use of oral diabetes agents other than metformin unless matched with controls
  • Type 1 diabetes
  • Chronic steroid use or use within the last 30 days
  • Significant liver disease including liver enzymes >3 x upper limit of normal range
  • Renal dysfunction defined as eGFR< 50mL/min/1.73m2
  • Significant cardiac disease such as heart transplantation
  • Significant gastrointestinal conditions that may interfere with drug absorption or GLP-1 release including bariatric surgery
  • Significant hematologic disease such as hematocrit <35%
  • Use of chronic anticoagulation
  • Severe pulmonary disease
  • Severe neurologic or psychiatric disease
  • Inability to comprehend study procedures

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Other
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Other: Crossover AB
Subjects in arm A will first receive placebo daily for 7 days in the first intervention followed by sitagliptin 100mg/d for 7 days in the crossover intervention.
Drug: Sitagliptin 100mg
Sitagliptin will be administered daily for 7 days, with a study day on day 7.
Other Names:
  • Januvia
Drug: Placebo Oral Tablet
Placebo will be administered daily for 7 days, with a study day on day 7.
Other: Crossover BA
Subjects in arm B will first receive sitagliptin 100mg/d for 7 days in the first intervention followed by placebo for 7 days in the crossover intervention.
Drug: Sitagliptin 100mg
Sitagliptin will be administered daily for 7 days, with a study day on day 7.
Other Names:
  • Januvia
Drug: Placebo Oral Tablet
Placebo will be administered daily for 7 days, with a study day on day 7.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Dipeptidyl peptidase 4 (DPP4)
Time Frame: during study days 1 and 2
DPP4 activity and antigen concentration
during study days 1 and 2

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Glucose Area Under the Curve
Time Frame: Before the meal and for 4 hours after (t=-15 through t=240 min) on study days 1 and 2
Glucose will be measured before after the mixed meal during sitagliptin and placebo. Area under the curve will be calculated based on at least 10 time points after the meal.
Before the meal and for 4 hours after (t=-15 through t=240 min) on study days 1 and 2
Disposition index
Time Frame: Calculated from samples collected before the meal and for 4 hours after (t=-15 through t=240 min) on study days 1 and 2
Disposition index will be calculated from insulin sensitivity and insulin secretion. These variables will be computed using mathematical modeling of insulin and c-peptide. We will collect insulin and c-peptide at least 10 time points after the meal.
Calculated from samples collected before the meal and for 4 hours after (t=-15 through t=240 min) on study days 1 and 2
Mean blood pressure
Time Frame: Before the meal and for 4 hours after (t=-15 through t=240 min) on study days 1 and 2
Measured via an automated blood pressure cuff approximately every 15 minutes
Before the meal and for 4 hours after (t=-15 through t=240 min) on study days 1 and 2
Glucagon-like peptide-1 (GLP-1)
Time Frame: Before the meal and for 4 hours after (t=-15 through t=240 min) on study days 1 and 2
This is released in response to a meal and rapidly degraded by DPP4. We will collect samples for at least six time points after the meal.
Before the meal and for 4 hours after (t=-15 through t=240 min) on study days 1 and 2
CD26
Time Frame: Before the meal or at baseline (t=-15 or -1 min) on study days 1 and 2
CD26 is DPP4 on T cells and monocytes.
Before the meal or at baseline (t=-15 or -1 min) on study days 1 and 2
Surrogate markers of lipolysis
Time Frame: Before the meal and for 4 hours after (t=-15 through t=240 min) on study days 1 and 2
Triglycerides, free fatty acids; We will collect samples at least six time points after the meal.
Before the meal and for 4 hours after (t=-15 through t=240 min) on study days 1 and 2
Mean heart rate
Time Frame: Before the meal and for 4 hours after (t=-15 through t=240 min) on study days 1 and 2
Measured via an automated blood pressure cuff approximately every 15 minutes
Before the meal and for 4 hours after (t=-15 through t=240 min) on study days 1 and 2

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Pennsylvania

Investigators

  • Principal Investigator: Jessica R Wilson, MD, MS, University of Pennsylvania

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

August 26, 2020

Primary Completion (Actual)

February 27, 2025

Study Completion (Estimated)

February 28, 2026

Study Registration Dates

First Submitted

March 25, 2019

First Submitted That Met QC Criteria

March 25, 2020

First Posted (Actual)

March 26, 2020

Study Record Updates

Last Update Posted (Estimated)

January 16, 2026

Last Update Submitted That Met QC Criteria

January 15, 2026

Last Verified

January 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 834482

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Results will be deidentified for outcomes of interest from this pilot study.

IPD Sharing Time Frame

Deidentified data will become available upon completion of the pilot study

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP
  • ICF

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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