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

NCT ID: NCT01439854

Last Updated: 2025-07-03

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 18 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-03-31
• Study Completion Date: 2018-06-30

Brief Summary

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].

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.

Conditions

Insulin Sensitivity; Multiple Mitochondrial Dysfunctions Syndrome

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: DOUBLE

Study Groups

Placebo

this arm is control

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Patients are treated with placebo

Dapagliflozin

Interventional arm

Group Type: EXPERIMENTAL

Dapagliflozin

Intervention Type: DRUG

Treatment arm, 10 mg per day for 2 weeks

Interventions

Dapagliflozin

Treatment arm, 10 mg per day for 2 weeks

Intervention Type: DRUG

Placebo

Patients are treated with placebo

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• T2DM
• Drug Naive Or On Oral Therapy

Exclusion Criteria

• Insulin Treatment
• Major Organ Disease

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

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

NIH

Sponsor Role: collaborator

The University of Texas Health Science Center at San Antonio

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Ralph DeFronzo, MD

Role: PRINCIPAL_INVESTIGATOR

The University of Texas Health Science Center at San Antonio

Devjit Tripathy, MD

Role: PRINCIPAL_INVESTIGATOR

The University of Texas Health Science Center at San Antonio

Locations

Diabetes Division, UTHSCSA

San Antonio, Texas, United States

Countries

United States

References

Daniele G, Xiong J, Solis-Herrera C, Merovci A, Eldor R, Tripathy D, DeFronzo RA, Norton L, Abdul-Ghani M. Dapagliflozin Enhances Fat Oxidation and Ketone Production in Patients With Type 2 Diabetes. Diabetes Care. 2016 Nov;39(11):2036-2041. doi: 10.2337/dc15-2688. Epub 2016 Aug 25.

Reference Type: RESULT

PMID: 27561923 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

R01DK024092

Identifier Type: NIH

Identifier Source: secondary_id

View Link

5 R01 DK024092-27/NIH Prot IV

Identifier Type: -

Identifier Source: org_study_id