Empagliflozin Reversal of Arterial StiffnEss in Aging

The investigators will employ a double-blinded randomized placebo control trial to determine the effects of 12 weeks of sodium glucose co-transporter 2 (SGLT2) inhibition with empagliflozin (10 mg daily), or matching placebo. Empagliflozin has been shown to decrease cardiovascular events and arterial stiffness in different populations. Placebo will be included for comparison purposes as empagliflozin is not a standard therapy for aging-associated arterial stiffness.

Inclusion criteria

• Able to provide consent
• 60 to 80 years of age at randomization (women must be postmenopausal defined as more than 1 year without menses)
• Stable anti-hypertensive medication regimen (if in use) for at least 90 days
• Evidence of arterial stiffening (defined as carotid-femoral PWV >/= 8 m/s) at the time of screening visit.

Exclusion criteria

• Diabetes
• BMI>/= 45kg/m2
• Known history of cardiovascular disease: heart failure, ischemic heart disease, peripheral artery disease or stroke
• Estimated glomerular filtration rate GFR < 29 mL/min
• Active cancer (excluding basal cell carcinoma or stage 1 squamous cell carcinoma of the skin)
• Excessive alcohol consumption (>14 drinks/week for men, >7 drinks/week for women)
• Use of hormone replacement therapy
• Body weight change ≥10% within the last 6 months
• Uncontrolled hypertension during screening visit (>180/110 mmHg)
• Symptomatic hypotension and/or a SBP <100 mmHg
• History of ketoacidosis
• High fall risk per assessment of study physician and/or safety officer at the time of screening (results must be abnormal for both fall risk assessments and orthostatic blood pressure measurements)
• Anticipated need of prolonged fasting
• History of recurrent UTIs or mycotic genital infections
• Following a low-carbohydrate diet (<20 grams/day)
• Participation in regular exercise > 3 days/week per week at a moderate or vigorous intensity
• Known sensitivity to nitrate medications