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.



Eligible Ages
Between 18 Years and 80 Years
Eligible Genders
Accepts Healthy Volunteers

Inclusion Criteria

  • Type 2 Diabetes Mellitus - Class II-III New York Heart Association (NYHA) heart failure and reduced ejection fraction (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 - Stable body weight (±4 pounds) over the last 3 months

Exclusion Criteria

  • Subjects treated with an SGLT2 inhibitor, a glucagon-like peptide-1 receptor agonist (GLP-1 RA) or pioglitazone - Resting heart rate >120 bpm - Systolic BP>180mmHg and/or diastolic BP >100mmHg - Resting percentage of blood oxygen saturation (SpO2) < 85% - Physical disability preventing safe performance of the exercise protocol.

Study Design

Early Phase 1
Study Type
Intervention Model
Parallel Assignment
Intervention Model Description
A randomized (2:1) placebo controlled double blind study
Primary Purpose
Basic Science
Double (Participant, Investigator)
Masking Description
Participants and investigators will be blinded to the randomization.

Arm Groups

ArmDescriptionAssigned Intervention
Empagliflozin Group
Subjects will be randomized 2:1 to receive empagliflozin, 25mg/day for 3 months
  • Drug: Empagliflozin 25 MG
    Empagliflozin 25MG will be administered orally once per day for 3 months
    Other names:
    • Jardiance
Placebo Comparator
Placebo group
Subjects will be randomized to receive the empagliflozin placebo for 3 months
  • Drug: Placebo
    The placebo will be administered orally once per day for 3 months
    Other names:
    • Placebo for Empagliflozin

Recruiting Locations

Texas Diabetes Institute - University Health System
San Antonio, Texas 78207
Yuejuan Qin, PhD

University of Texas Health Science Center at San Antonio
San Antonio, Texas 78229
Carolina Solis-Herrera, MD

More Details

The University of Texas Health Science Center at San Antonio

Study Contact

Carolina Solis-Herrera, MD

Detailed 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.


Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.