Effects of Empagliflozin on Cardiac Microvasculature and Insulin Sensitivity in Subjects With Type 2 Diabetes

Study Overview
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Brief Summary
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The aim is to test in T2DM patients, whether, compared to placebo, 12 weeks of SGLT-2 inhibitor improves post-absorptive, post-insulin infusion or postprandial insulin action to enhance Cardiac Muscle vascular function and whether changes correlate with improved GV or postprandial hyperglycemia

Detailed Description
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The investigators will study 32 T2DM subjects measuring cardiac muscle vascular function before and after a 4 hour insulin clamp ( protocol A) and before and after a mixed meal (protocol B). Then subjects will be randomized into 2 groups: Group 1 will undergo a 12 week intervention of Empagliflozin, and Group 2 will do 12 weeks of Placebo. The intervention will be single blinded. At the end of the 12 week intervention subjects will repeat protocol A and B. The study's primary objective is to assess whether, compared to placebo, 12 weeks of Empagliflozin improves post-absorptive or postprandial insulin action to enhance myocardial perfusion (MP) and whether changes of MP correlate with improved glucose variability or postprandial hyperglycemia

Official Title
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Effects of Empagliflozin on Cardiac Microvasculature and Insulin Sensitivity in Subjects With Type 2 Diabetes

Conditions
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Type2 Diabetes, Insulin Sensitivity

Intervention / Treatment
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* Drug: Empagliflozin 25 MG


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: A1C > 6.5 and <9% Never on SGLT-2i (eg: Jardiance, Invokana, Farxiga, Steglatro) On stable dose of oral hypoglycemic agents >3 months On stable dose of other medications for >3 months BMI-<35 Exclusion Criteria: • Smoking presently or in the past 6 months Taking insulin BP >160/90 BMI >35 History of congestive heart failure, ischemic heart disease, severe pulmonary disease, liver or kidney disease. Any vascular disease such as myocardial infarction, stroke, peripheral vascular disease History of cancer or psychiatric disease Presence of an intracardiac or intrapulmonary shunt (we will screen for this by auscultation during the physical exam by PI). Pregnant or breastfeeding. Known hypersensitivity to perflutren (contained in Definity) Screening O2 saturation <90% History of recurrent UTI/bladder/kidney infections-eGFR is below 45 mL/min/1.73.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Empagliflozin + insulin infusion<br>vascular measurements in overnight fasted state and during insulin infusion | Drug: Empagliflozin 25 MG<br>* SGLT-2 inhibitor<br>|
| Active Comparator: Empagliflozin + mixed meal<br>vascular measurements in overnight fasted state and 2 hours after mixed meal 10kcal/kg body weight ( 55% Cho, 30%Fat, 20% Pro) | Drug: Empagliflozin 25 MG<br>* SGLT-2 inhibitor<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Myocardial microvascular perfusion | Vascular measure of myocardial perfusion | Between baseline and 12 weeks treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Flow Mediated Dilation (FMD) Vascular measure of conduit artery stiffness Change in Flow Mediated Dilation (FMD) between baseline and after 2 hour insulin clamp Vascular measure of conduit artery stiffness Flow Mediated Dilation ( FMD) | Vascular measure of conduit artery stiffness | Between baseline and 12 weeks of treatment. | 
| Augmentation Index ( AI) | Measurement of central artery stiffness | Between baseline and 12 weeks of treatment. | 
| Pulse Wave Velocity ( PWV) | Measurement of central artery stiffness | Between baseline and 12 weeks of treatment |