Ketones, Muscle Metabolism, and SGLT2 Inhibitors
The University of Texas Health Science Center at San Antonio
Summary
The study team will examine the effects of elevated plasma ketone levels following initiation of SGLT2 inhibitor therapy in high-risk type 2 diabetes mellitus (T2DM) individuals with heart failure (HF) with reduced ejection fraction (HFrEF) providing an energy-rich fuel that is taken up with great avidity by the myocardium, to measure change in Left Ventricle diastolic and systolic function
Description
The study team will examine the 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 quantify 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 phosp…
Eligibility
- Age range
- 18–70 years
- Sex
- All
- Healthy volunteers
- No
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 s…
Interventions
- DrugEmpagliflozin 25 MG Oral Tablet
Empagliflozin 25MG will be administered orally once per day for 3 months
- DrugPlacebo
The placebo will be administered orally once per day for 3 months
- DrugAcipimox 250 Mg Oral Capsule
subjects will be started on acipimox 250mg every 6 hours for 8 days while on continued empagliflozin/placebo therapy. This will be added at the end of 3 months after they finished baseline studies
Location
- Texas Diabetes Institute - University Health SystemSan Antonio, Texas