Can Exenatide Prevent Increase in EGP in Response to Dapagliflozin-induced Increase in Glucosuria

NCT03331289 | Completed Phase 4 Results FDA Drug

• 2 other identifiers: HSC20170582HR01DK107680
• Study Type: interventional
• Target: 107
• Locations: 1 country
• Sites: 1

Brief Summary

Research Design/Plan: After screening, each subject will receive 1 measurements of Endogenous Glucose Production \[EGP\] with prime-continuous Infusion of 3-3H-glucose. After completing the EGP measurement each subject will receive a Double Tracer Oral Glucose Tolerance Test \[OGTT\]. Methods: Visit 1: Screening. Medical history will be obtained, physical exam performed, and pregnancy test performed. Visit 2: Endogenous Glucose Production Measurement: The rate of EGP will be measured with 3-3H-glucose. Visit 3: Double Tracer OGTT

Conditions

Diabetes Mellitus, Type 2

Outcome Measures

Primary Outcomes (1)

• Change in EGP From Baseline to Post-oral Glucose Load.

  The difference in rate of EGP during the last hour of the study (from 240-300 minutes) between drug-treatment and placebo treatment studies represents the effect of drug treatment on EGP, which will be compared among the 3 acute drug treatments (exenatide; dapagliflozin; exenatide plus dapagliflozin this data includes change in EGP above baseline following dapagliflozin alone vs dapagliflozin/exenatide) with ANOVA.

  From baseline [-35 to 0min] to the last hour post-glucose load [240-300 minutes]

Study Arms (4)

Placebo

PLACEBO COMPARATOR

we will examine whether the coadministration of exenatide plus dapagliflozin will prevent the increase in EGP and result in an additive or even synergistic decrease in plasma glucose conc compared to each agent alone.

Drug: Placebo

Exenatide

ACTIVE COMPARATOR

we will examine whether the coadministration of exenatide plus dapagliflozin will prevent the increase in EGP and result in an additive or even synergistic decrease in plasma glucose conc compared to each agent alone.

Drug: Exenatide

Dapagliflozin

ACTIVE COMPARATOR

we will examine whether the coadministration of exenatide plus dapagliflozin will prevent the increase in EGP and result in an additive or even synergistic decrease in plasma glucose conc compared to each agent alone.

Drug: Dapagliflozin

Exenatide and Dapagliflozin

ACTIVE COMPARATOR

we will examine whether the coadministration of exenatide plus dapagliflozin will prevent the increase in EGP and result in an additive or even synergistic decrease in plasma glucose conc compared to each agent alone.

Drug: Exenatide and Dapagliflozin

Interventions

Placebo DRUG

Placebo will be administered to 20 subjects after a 3 hour tracer equilibration period

Also known as: Placebo drug

Placebo

Exenatide DRUG

Exenatide will be administered to 20 subjects after a 3 hour tracer equilibration period

Also known as: Byetta, Bydureon

Exenatide

Dapagliflozin DRUG

Dapagliflozin will be administered to 20 subjects after a 3 hour tracer equilibration period

Also known as: Farxiga

Dapagliflozin

Exenatide and Dapagliflozin DRUG

Exenatide and Dapagliflozin will be administered to 20 subjects after a 3 hour tracer equilibration period

Also known as: Byetta plus Dapagliflozin

Exenatide and Dapagliflozin

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Health Status: Type 2 Diabetes Mellitus according to ADA criteria (subjects must be in good general health as determined by physical exam, medical history, blood chemistry-CBC, TSH, T4, EKG and urinalysis)
• BMI: 21-45kg/m
• HbA1C\>7.0% and \<10.5%
• Medication: Drug naïve and/or on a stable dose of metformin and/or sulfonylurea (more than 3 months)

You may not qualify if:

• Health Status: Type 1 Diabetics
• Proliferative diabetic retinopathy
• Plasma Creatinine greater than 1.4mg/dL in females or greater than 1.5mg/dL in males, or 24 hour urine albumin excretion greater than 300mg/dL
• Medication: Subjects taking drugs known to affect glucose metabolism (other than metformin and sulfonylurea)

Sponsors & Collaborators

• The University of Texas Health Science Center at San Antonio: lead
• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): collaborator

Study Sites (1)

University Health System Texas Diabetic Institute

San Antonio, Texas, 78207, United States

Location

Related Publications (1)

• Alatrach M, Agyin C, Solis-Herrera C, Lavryneko O, Adams J, Gastaldelli A, Triplitt C, DeFronzo RA, Cersosimo E. Dapagliflozin Impairs the Suppression of Endogenous Glucose Production in Type 2 Diabetes Following Oral Glucose. Diabetes Care. 2022 Jun 2;45(6):1372-1380. doi: 10.2337/dc21-1798.

  PMID: 35235659 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Interventions

Exenatide; dapagliflozin

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Peptides; Amino Acids, Peptides, and Proteins; Venoms; Complex Mixtures; Toxins, Biological; Biological Factors

Results Point of Contact

• Title: Ralph A DeFronzo
• Organization: UTexas_SanAntonio

defronzo@uthscsa.edu

2105676691

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Participants will be randomized to one of four groups (20 per group): i) placebo; (ii) exenatide 5 ug subcutaneously; (iii) dapagliflozin (10 mg); and (iv) dapagliflozin 10 mg plus exenatide 5 ug

Study Record Dates

• First Submitted: October 31, 2017
• First Posted: November 6, 2017
• Study Start: February 28, 2018
• Primary Completion: March 31, 2022
• Study Completion: November 4, 2022
• Last Updated: July 24, 2023
• Results First Posted: July 24, 2023

Record last verified: 2023-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Data will be shared once study closes to enrollment and all data are analyzed and published. Informed consent documentation will be available for sharing.....
• Access Criteria: Access will be available through the journal website and on request through the PI.

Locations

US (1)