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Completed

NCT Number: NCT01439854

Study of Dapagliflozin on Mitochondrial Dysfunction and Impaired Insulin Signaling/Action

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].

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Key information

Conditions

Insulin Sensitivity Female Urogenital Diseases Female Urogenital Diseases and Pregnancy Complications Glucose Metabolism Disorders Glycosuria Hyperinsulinism Insulin Resistance Male Urogenital Diseases Metabolic Diseases Multiple Mitochondrial Dysfunctions Syndrome Nutritional and Metabolic Diseases Urination Disorders Urogenital Diseases Urologic Diseases

Age range

18 year–70 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Diabetes Division, UTHSCSA

San Antonio, Texas, 78229, United States

About this study

"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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • T2DM
  • Drug Naive Or On Oral Therapy

Exclusion criteria

  • Insulin Treatment
  • Major Organ Disease

Treatment and study plan

Dapagliflozin

Drug

Treatment arm, 10 mg per day for 2 weeks

Placebo

Drug

Patients are treated with placebo

Primary outcomes

  1. 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

Secondary outcomes

  1. 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.

Sponsors and collaborators

Lead sponsor

The University of Texas Health Science Center at San Antonio

Other

Collaborators

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

Registry information

Official study title

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

Acronym: DAPA MITO

Important dates

Study start
2011
Primary completion
2018
Study completion
2018
First posted
Sep 23, 2011
Registry last updated
Jul 3, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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