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Clinical trial Recruiting at 1 site Early Phase 1 Interventional Ages 18 to 70

SGLT2 medication and ketone effects on heart function in people with type 2 diabetes and reduced ejection fraction

Official title: Ketones, Muscle Metabolism, and SGLT2 Inhibitors

Run by The University of Texas Health Science Center at San Antonio · NCT06229678 · Data updated 2026-11-12

This will test whether taking empagliflozin, which raises blood ketones, helps the heart pump and fill better in adults with type 2 diabetes and heart failure with reduced ejection fraction.

Quick facts

PhaseEarly Phase 1
Study typeInterventional
Ages18 Years to 70 Years
SexAll
Enrollment71 (estimated)
SponsorThe University of Texas Health Science Center at San Antonio
Academic / other
Locations1 site (San Antonio, Texas)
StatusRecruiting
StartedJanuary 25, 2024
Main results expectedNovember 1, 2026
Study endsMarch 1, 2027
Registry record updatedFebruary 5, 2026
Trial IDNCT06229678 on ClinicalTrials.gov

Is this trial a fit for you?

Likely a good fit

Adults age 18–80 with type 2 diabetes, NYHA class II–III heart failure with reduced ejection fraction (<50%), BMI 23–44 kg/m2, HbA1c 6.0–10.0%, eGFR ≥30 ml/min/1.73 m2, and on allowed diabetes treatments are ideal candidates.

Probably not a fit

Patients without type 2 diabetes, with preserved ejection fraction, with excluded cardiac conditions (eg, restrictive cardiomyopathy, active myocarditis, severe valvular disease), with eGFR <30, or outside the BMI/HbA1c limits are unlikely to qualify or benefit from the specific questions this study addresses.

A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.

What this trial studies

Adults with type 2 diabetes and NYHA class II–III heart failure will take empagliflozin for 12 weeks while investigators measure changes in heart and muscle energetics. Cardiac MRI will be used to quantify left ventricular systolic and diastolic function, and muscle 31P- and 1H-MRS will measure phosphocreatine, ATP, and intramyocellular lipids before and after treatment. To isolate the role of elevated ketones, the study will block the empagliflozin-induced ketone rise with acipimox in a controlled intervention while continuing empagliflozin. Patient-reported symptoms will be tracked with the Kansas City Cardiomyopathy Questionnaire to relate physiologic changes to quality of life.

Why it matters

Potential benefit: If successful, the approach could improve heart function and symptoms by showing that SGLT2-induced ketones provide an energy source for the failing heart and guide targeted therapies.

How similar studies have gone: Large trials have shown SGLT2 inhibitors reduce heart failure events, but directly testing whether ketone increases explain those benefits is a relatively novel and less-tested approach.

Who can join: the full rules

Show full inclusion / exclusion criteria 
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 23-44 kg/m2
* Glycated hemoglobin (HbA1c) 6.0-10.0%
* Blood Pressure (BP) ≤ 145/85 mmHg
* Estimated glomerular filtration rate (eGFR) ≥30 ml/min•1.73 m2
* Only Type 2 diabetics treated with diet/exercise, metformin, sulfonylureas, metformin/sulfonylurea, Glucagon-like peptide-1 receptor agonist (GLP-1 RA), or insulin
* Stable body weight (±4 pounds) over the previous 3 months prior to enrollment
* Ability to understand study procedures and to comply with them for the entire length of the study.

Exclusion Criteria:

* Heart failure due to restrictive cardiomyopathy, active myocarditis, constrictive pericarditis, severe valvular heart disease, hypertrophic obstructive cardiomyopathy.
* Significant change in diuretic management during the month prior to screening (defined by doubling of diuretic dose or addition of another heart failure medication)
* Type 2 Diabetics treated with Dipeptidyl Peptidase-4 Inhibitor (DPP4i) or pioglitazone
* Pregnancy, lactation, or plans to become pregnant. A negative pregnancy test will be performed before each MRI study to assess current status. For women of child-bearing age (WOCBA) willingness to use contraception, if applicable.
* Allergy/sensitivity to study drugs or their ingredients.
* Cancer.
* Current drug or alcohol use or dependence that, in the opinion of the site investigator, would interfere with adherence to study requirements.
* Inability or unwillingness of individual or legal guardian/representative to give written informed consent.

Where it's running

  • Texas Diabetes Institute - University Health System
    San Antonio, Texas, United States     Recruiting

Study contacts

  • Principal investigator: Ralph DeFronzo, MD — The University of Texas Health Science Center at San Antonio
  • Study coordinator: Ralph DeFronzo, MD
  • Email: defronzo@uthscsa.edu
  • Phone: 210-567-6691

Similar studies

Other studies for the same condition or treatment. Recruiting studies are listed first.

How to take part

  1. Review the eligibility criteria above with your treating physician.
  2. Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
  3. Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.
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Last reviewed 2026-11-14 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.