Ertugliflozin: Cardioprotective Effects on Epicardial Fat

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to learn if Sodium-Glucose Cotransporter 2 inhibitor (SGLT2i) medications enhance beneficial properties of epicardial adipose tissue including metabolic flexibility, insulin sensitivity, decreased cell size and reduced inflammation.

Official Title
-----------------
Ertugliflozin: Cardioprotective Effects on Epicardial Fat

Conditions
-----------------
Cardiovascular Diseases, Atherosclerosis, Type 2 Diabetes, Insulin Resistance

Intervention / Treatment
-----------------
* Drug: Ertugliflozin
* Drug: Glipizide


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: patient at Stanford Cardiovascular Surgery clinic who is scheduled for cardiac bypass surgery history of Diabetes Mellitus Type 2 currently taking metformin or diet-controlled Exclusion Criteria: allergy or intolerance to interventional medication currently taking any anti-diabetic medication other than metformin

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: unblinded randomized trial
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ertugliflozin<br>Ertugliflozin, also known as Steglatro, will be administered once daily for 5 days at a dose of 15mg orally. | Drug: Ertugliflozin<br>* Consenting participants in the Ertugliflozen group will be supplied with 2-week course of medication prior to cardiac surgery. Participants will be educated on use and have blood glucose monitored during the medication course. The surgeon will then collect a small amount of fat near the heart during surgery.<br>* Other names: SGLT2 inhibitor;|
| Active Comparator: Glipizide<br>Glipizide will be randomized to either 2.5mg or 5mg oral dose once daily for 5 days. | Drug: Glipizide<br>* Consenting participants in the Glipizide group will be supplied with 2-week course of medication prior to cardiac surgery. Participants will be educated on use and have blood glucose monitored during the medication course. The surgeon will then collect a small amount of fat near the heart during surgery.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of isoproterenol-stimulated lipolysis to measure metabolic flexibility in epicardial adipose tissue samples. | Analysis will be performed using Lipolysis Colorimetric Assay and measured by glycerol content on standard curve. Indirect effects of SGLT2i in vivo in epicardial adipose tissue will be compared to Glipizide by measuring rate of lipolysis, or breakdown of adipose in to free fatty acids. | Time to collect tissue collected during surgery (up to 15 minutes) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Average insulin mediated glucose uptake (IMGU) to measure insulin sensitivity in epicardial adipose tissue samples. | Mature adipocytes will be isolated, cultured, and treated with 2-NBDG, a fluorescently-labeled deoxyglucose analog, as a probe for the detection of glucose uptake measured by excitation/emission of florescence in the mature cells. | Time to collect tissue collected during surgery (up to 15 minutes) | 
| Characterization of the inflammatory cytokine expression profile in epicardial adipose tissue samples. | Analysis will be performed using Luminex to measure levels of inflammatory cytokines on the human adipocyte panel. | Time to collect tissue collected during surgery (up to 15 minutes) | 
| Distribution of adipose cell size in epicardial tissue. | After tissue collection and osmium fixation, adipose cell size will be determined by Beckman Coulter Multisizer III, and described via a mathematical model to estimate peak diameter, fat storage capacity, size variability, and % small cells. | Time to collect tissue collected during surgery (up to 15 minutes) | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Epicardial Adipose Tissue, SGLT2 Inhibitor