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

Early Phase 1

• Conditions: Type2 Diabetes; Insulin Sensitivity
• Interventions: Drug: Empagliflozin 25 MG

• Registration Number: NCT04203927
• Lead Sponsor: University of Virginia

Brief Summary

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

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

Study Timeline

• Study First Submitted: 2019-12-17
• Study First Submitted QC: 2019-12-17
• Study First Posted: 2019-12-18
• Study Start: 2020-02-01
• Status Verified: 2022-02
• Last Update Submitted: 2022-02-09
• Last Update Posted: 2022-02-10
• Primary Completion: 2023-10-30
• Study Completion: 2023-11-30

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 50

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Empagliflozin + insulin infusion	Empagliflozin 25 MG	vascular measurements in overnight fasted state and during insulin infusion
Empagliflozin + mixed meal	Empagliflozin 25 MG	vascular measurements in overnight fasted state and 2 hours after mixed meal 10kcal/kg body weight ( 55% Cho, 30%Fat, 20% Pro)

Primary Outcome Measures

Name	Time	Method
Myocardial microvascular perfusion	Between baseline and 12 weeks treatment	Vascular measure of myocardial perfusion

Secondary Outcome Measures

Name	Time	Method
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)	Between baseline and 12 weeks of treatment.	Vascular measure of conduit artery stiffness
Augmentation Index ( AI)	Between baseline and 12 weeks of treatment.	Measurement of central artery stiffness
Pulse Wave Velocity ( PWV)	Between baseline and 12 weeks of treatment	Measurement of central artery stiffness

Trial Locations

Locations (1)

University of Virginia; 🇺🇸 Charlottesville, Virginia, United States