Ertugliflozin: Cardioprotective Effects on Epicardial Fat

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.

Study Overview

• Status: Completed
• Conditions: Cardiovascular Diseases; Atherosclerosis; Insulin Resistance; Type 2 Diabetes
• Intervention / Treatment: Drug: Ertugliflozin

• Study Type: Interventional
• Enrollment (Actual): 61
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Stanford, California, United States, 94305
      • Stanford University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• patient at Stanford Cardiovascular Surgery clinic who is scheduled for cardiac bypass surgery or vascular surgery
• history of Diabetes Mellitus Type 2 currently diet controlled, or on metformin or dpp4 inhibitors

Exclusion Criteria:

• allergy or intolerance to interventional medication
• currently taking insulin, glp-1 inhibitors, or sulfonylureas

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Ertugliflozin (treated tissue); Adipose tissue samples collected from participants were treated with Ertugliflozin at a concentration of 25 µM in vitro. Tissue samples were incubated with Ertugliflozin to evaluate its effects on lipolysis, inflammation, and gene expression in epicardial, pericardial, and subcutaneous adipose tissues	Drug: Ertugliflozin; Adipose tissue samples collected from participants were treated with Ertugliflozin at a concentration of 25 µM in vitro. This treatment was applied in a laboratory setting to assess the effects of Ertugliflozin on lipolysis, inflammatory cytokine release, and gene expression in epicardial, pericardial, and subcutaneous adipose tissue; Other Names: SGLT2 inhibitor

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of Isoproterenol-Stimulated Lipolysis in Adipose Tissue Depots to Measure Metabolic Flexibility	The rate of lipolysis was measured under basal, isoproterenol-stimulated, and insulin-suppressed conditions in adipose tissue depots (epicardial, pericardial, and subcutaneous) treated with and without Ertugliflozin. Lipolysis was quantified using a colorimetric assay to determine metabolic flexibility. Cardiac adipose tissue explants cultured with ertugliflozin compared to mock condition.	Time to collect tissue collected during surgery (up to 15 minutes)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cytokine Secretion Profiles in Adipose Tissue Depots	Levels of cytokines, including MCP1, TNF-β, IL-6, IFN-γ, and IL1-β, were measured in the culture medium of treated and untreated adipose tissue depots (epicardial, pericardial, and subcutaneous) using Luminex assays. Cytokine levels were used to characterize inflammation and response to Ertugliflozin treatment in cardiac adipose tissue explants) and isolated adipocytes after culture with Ertugliflozin vs mock condition.	Time to collect tissue collected during surgery (up to 15 minutes)
Adipose Cell Size Distribution in Pericardial and Subcutaneous Tissue	Adipose cell size distribution was assessed in subcutaneous and pericardial adipose tissue samples using osmium fixation and cell diameter measurements. The relationship between cell size and Ertugliflozin treatment was analyzed.	Time to process tissue samples collected during surgery (up to 15 minutes).

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Gene Expression Profiles in Adipose Tissue Depots	Expression of genes related to inflammation and lipid metabolism (e.g., MCP1, TNF-β, IL-6) was measured in adipose tissue samples using mRNA extraction and RT-PCR after Ertugliflozin treatment. Analysis was performed to evaluate molecular changes in adipose depots (epicardial, pericardial, and subcutaneous).	Time to collect tissue collected during surgery (up to 15 minutes)

Collaborators and Investigators

• Sponsor: Stanford University
• Collaborators: Merck Sharp & Dohme LLC
• Investigators: Principal Investigator: Tracey McLaughlin, MD, Stanford University

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2020
• Primary Completion (Actual): December 31, 2023
• Study Completion (Actual): December 31, 2023

Study Registration Dates

• First Submitted: November 15, 2019
• First Submitted That Met QC Criteria: November 15, 2019
• First Posted (Actual): November 19, 2019

Study Record Updates

• Last Update Posted (Actual): June 4, 2026
• Last Update Submitted That Met QC Criteria: May 9, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: SGLT2 Inhibitor; Epicardial Adipose Tissue
• Additional Relevant MeSH Terms: Endocrine System Diseases; Vascular Diseases; Metabolic Diseases; Glucose Metabolism Disorders; Diabetes Mellitus; Hyperinsulinism; Arteriosclerosis; Arterial Occlusive Diseases; Nutritional and Metabolic Diseases; Diabetes Mellitus, Type 2; Cardiovascular Diseases; Insulin Resistance; Atherosclerosis; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Hypoglycemic Agents; Pharmacologic Actions; Chemical Actions and Uses; Sodium-Glucose Transporter 2 Inhibitors; ertugliflozin
• Other Study ID Numbers: 52647

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No