Effects of Empagliflozin on Cardiac Microvasculature and Insulin Sensitivity in Subjects With Type 2 Diabetes (EJB051)

University of Virginia

Status and phase: Unknown; Early Phase 1

Conditions: Type2 Diabetes; Insulin Sensitivity

Treatments: Drug: Empagliflozin 25 MG

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT04203927

1R01HL142250-01A1 (U.S. NIH Grant/Contract)

21403

Details and patient eligibility

About

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

Full 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

Enrollment: 50 estimated patients

Sex: All

Ages: 18 to 60 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Basic Science

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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50 participants in 2 patient groups

Empagliflozin + insulin infusion

Active Comparator group

Description:

vascular measurements in overnight fasted state and during insulin infusion

Treatment:

Drug: Empagliflozin 25 MG

Empagliflozin + mixed meal

Active Comparator group

Description:

vascular measurements in overnight fasted state and 2 hours after mixed meal 10kcal/kg body weight ( 55% Cho, 30%Fat, 20% Pro)

Treatment:

Drug: Empagliflozin 25 MG