SGLT2 medication and ketone effects on heart function in people with type 2 diabetes and reduced ejection fraction
Ketones, Muscle Metabolism, and SGLT2 Inhibitors
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
| Phase | Early Phase 1 |
|---|---|
| Study type | Interventional |
| Enrollment | 71 (estimated) |
| Ages | 18 Years to 70 Years |
| Sex | All |
| Sponsor | The University of Texas Health Science Center at San Antonio Academic / other |
| Locations | 1 site (San Antonio, Texas) |
| Trial ID | NCT06229678 on ClinicalTrials.gov |
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.
Who should consider this trial
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.
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.
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 performed: 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.
Eligibility criteria
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 this trial is running
San Antonio, Texas
- 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
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.