Study of Dapagliflozin on Mitochondrial Dysfunction and Impaired Insulin Signaling/Action (DAPA MITO)

June 16, 2025 updated by: The University of Texas Health Science Center at San Antonio

Regulation of Hepatic and Peripheral Glucose Metabolism: Protocol IVA. Effect of Plasma Glucose Reduction by Selective SLGT2 Inhibition on Mitochondrial Dysfunction and Impaired Insulin Signaling/Sensitivity in T2DM

The purpose of this study is to examine the effect of the chronic treatment of type 2 diabetes (T2DM) with dapagliflozin on: (1) mitochondrial gene function/expression and insulin signaling/action and (2) oral glucose tolerance and beta cell function. Dapagliflozin is a potent, highly specific inhibitor of renal glucose transport [SGLT2].

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

"Glucotoxicity" has been implicated as a cause of insulin resistance and impaired beta cell function in T2DM. Abundant support for the glucotoxicity hypothesis has been provided by in vivo and in vitro studies in animals, but a rigorous test of this hypothesis in man is lacking. The investigators propose to test the glucotoxicity hypothesis by chronically reducing the plasma glucose in type 2 diabetic subjects (T2DM) with an inhibitor of renal glucose transport, dapaglifozin, and examining the effect of restoration of normoglycemia on mitochondrial function and insulin signaling/sensitivity. Lastly, the investigators will test the "glucolipotoxicity" hypothesis, which states that the toxic effects of elevated plasma FFA on insulin sensitive tissues (i.e., muscle) are magnified in the presence of concurrent hyperglycemia. Thus, high glucose levels increase malonyl CoA, which inhibits CPT I, leading to accumulation of FACoA/DAG, which impair mitochondrial function and inhibit insulin action.

Study Type

Interventional

Enrollment (Actual)

18

Phase

  • Not Applicable

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
    • Texas
      • San Antonio, Texas, United States, 78229
        • Diabetes Division, UTHSCSA

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 70 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • T2DM
  • Drug Naive Or On Oral Therapy

Exclusion Criteria:

  • Insulin Treatment
  • Major Organ Disease

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: Basic Science
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Placebo Comparator: Placebo
this arm is control
Drug: Placebo
Patients are treated with placebo
Experimental: Dapagliflozin
Interventional arm
Drug: Dapagliflozin
Treatment arm, 10 mg per day for 2 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in Insulin Sensitivity
Time Frame: baseline, two weeks
The change in insulin sensitivity and total glucose disposal measured at two weeks with the insulin clamp compared to baseline. This is measured using TGD (whole body tissue glucose disposal)/SSPI (steady state plasma insulin concentration) ratio
baseline, two weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in Mitochondrial Function
Time Frame: baseline, two weeks
The change in mitochondrial function/gene expression at two weeks compared to baseline. This was measured by energy expenditure.
baseline, two weeks

Collaborators and Investigators

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

Sponsor

The University of Texas Health Science Center at San Antonio

Collaborators

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Investigators

  • Principal Investigator: Ralph DeFronzo, MD, The University of Texas Health Science Center at San Antonio
  • Principal Investigator: Devjit Tripathy, MD, The University of Texas Health Science Center at San Antonio

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

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

March 1, 2011

Primary Completion (Actual)

June 30, 2018

Study Completion (Actual)

June 30, 2018

Study Registration Dates

First Submitted

August 3, 2011

First Submitted That Met QC Criteria

September 22, 2011

First Posted (Estimated)

September 23, 2011

Study Record Updates

Last Update Posted (Actual)

July 3, 2025

Last Update Submitted That Met QC Criteria

June 16, 2025

Last Verified

June 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 5 R01 DK024092-27/NIH Prot IV
  • R01DK024092 (U.S. NIH Grant/Contract)

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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