SGLT2 Inhibitors, Ketones, and Cardiovascular Benefit Research Plan

Last updated: March 25, 2025
Sponsor: The University of Texas Health Science Center at San Antonio
Overall Status: Active - Recruiting

Phase

1

Condition

Chest Pain

Congestive Heart Failure

Hyponatremia

Treatment

Empagliflozin 25 MG

Placebo

Clinical Study ID

NCT05057806
HSC20210528H
R01DK107680
2021176
  • Ages 18-80
  • All Genders

Study Summary

The study team will examine the effects of SGLT2i (and SGLT2i-induced increases in plasma ketone concentrations) on skeletal muscle and cardiac ketone uptake, skeletal muscle bioenergetics, cardiopulmonary exercise capacity, and patient-reported functional outcomes.

Eligibility Criteria

Inclusion

Inclusion Criteria:

  • Type 2 Diabetes Mellitus

  • Class II-III New York Heart Association (NYHA) heart failure and reduced ejectionfraction (EF) <50%

  • Age 18-80 years

  • BMI 23-38 kg/m2

  • Glycated hemoglobin (HbA1c) 5.5-10%

  • Blood Pressure (BP) ≤ 145/85 mmHg

  • Estimated glomerular filtration rate (eGFR) ≥30 ml/min•1.73 m2

  • Stable dose of guideline-directed medications for heart failure and Diabetes

  • Stable body weight (±4 pounds) over the last 3 months

  • Does not suffer from severe claustrophobia

  • No contraindication for MRI (metal plates, screws, shrapnel, pins, or cardiacpacemaker)

Exclusion

Exclusion Criteria:

  • Subjects treated with an SGLT2 inhibitor, a glucagon-like peptide-1 receptor agonist (GLP-1 RA) or pioglitazone

  • Pregnancy, lactation or plans to become pregnant

  • Allergy/sensitivity to study drugs or their ingredients

  • Cancer

  • Current drug or alcohol use or dependence

  • Inability or unwillingness of individual or legal guardian/representative to givewritten informed consent

Study Design

Total Participants: 30
Treatment Group(s): 2
Primary Treatment: Empagliflozin 25 MG
Phase: 1
Study Start date:
January 13, 2021
Estimated Completion Date:
March 31, 2027

Study Description

The study team will examine effects of elevated plasma ketones caused by 12-week treatment with an SGLT2i (empagliflozin) treatment in participants with T2DM and HF. The study team will focus on three possible mechanisms of action for these effects and test the following:

(i) Skeletal muscle bioenergetics. Using 31P-MRS, the team will quantitate phosphocreatine [PCr], ATP, inorganic phosphate, phosphodiester, and intracellular pH. With 1H-MRS, and will measure intramyocellular lipid content at rest and ATPmax production after exercise. The team will examine the relationships between phosphorous metabolite concentrations, intramyocellular lipid content, and ATP generation before and after 12 weeks of SGLT2 inhibition.

(ii) Cardiopulmonary functional capacity.

(iii) Improvements in Patient-Reported Outcomes (PRO). The Patient-Reported Outcomes Measure Information System (PROMIS) Item Bank v2.0 - Physical Function - Short Form 20a will be used to evaluate self-reported physical function and well-being. This tool is a well-developed and validated method to obtain patient self-reported parameters of health in adults.

Connect with a study center

  • Texas Diabetes Institute - University Health System

    San Antonio, Texas 78207
    United States

    Active - Recruiting

  • University of Texas Health Science Center at San Antonio

    San Antonio, Texas 78229
    United States

    Active - Recruiting

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