The Effect of SGLT2 Inhibition on Adipose Inflammation and Endothelial Function

Eligibility Criteria

• 1. Age 18 to 70 years old
• 2. Metabolic syndrome as defined by 3 or more of 5 criteria:
• 1. Systolic blood pressure ≥ 130 mmHg or diastolic blood pressure ≥ 85 mmg Hg or treatment with anti-hypertensive medications for minimum of 6 months
• 2. Triglycerides ≥ 150 mg/dL or treatment with a triglyceride-targeted medication (fenofibrate, gemfibrozil, niacin, high dose omega-3 fatty acids)
• 3. High-density lipoprotein (HDL) \< 40 mg/dL in males or \< 50 mg/dL in females
• 4. Fasting blood glucose ≥ 100mg/dL or treatment with glucose-lowering medications
• 5. Waist circumference ≥ 102 cm in males or ≥ 88cm in females
• 3. BMI ≥ 35 kg/M2
• 4. Scheduled gastric bypass or gastric sleeve in approximately 90 days (range 90-150 days)
• 5. The ability to provide informed consent
• 6. Type 1 diabetes.
• 7. Poorly controlled type 2 diabetes as defined by HbA1c ≥ 9%.
• 8. Use of anti-diabetic medications other than stable dose of metformin or a sulfonylurea in the last 1 month.
• 9. Treatment with a glucagon-like peptide-1 receptor agonist or co-agonist in the last 3 months.
• 10. Treatment with an SGLT2 inhibitor in the last 3 months.
• 11. Pregnancy or breast-feeding. Women of child-bearing potential will be required to have undergone surgical sterilization or to be using an intra-uterine device, hormonal contraceptive, or barrier methods of birth control.
• 12. Cardiovascular disease such as myocardial infarction within six months prior to enrollment, presence of angina pectoris, significant arrhythmia, congestive heart failure (left ventricular hypertrophy acceptable), deep vein thrombosis, pulmonary embolism, -second- or third-degree heart block, mitral valve stenosis, aortic stenosis, or hypertrophic cardiomyopathy
• 13. Presence of implanted cardiac defibrillator or pacemaker
• 14. History of serious neurologic disease such as cerebral hemorrhage, stroke, or transient ischemic attack
• 15. History of pancreatitis or pancreatic surgery
• 16. History or presence of immunological or hematological disorders
• 17. Clinically significant gastrointestinal impairment that could interfere with drug absorption
• 18. History of advanced liver disease with cirrhosis
• 19. Individuals with an eGFR\<45 mL/min/1.73 m2, where eGFR is determined by the four-variable Modification of Diet in Renal Disease (MDRD) equation, where serum creatinine is expressed in mg/dL and age in years: eGFR (mL/min/1.73m2)=186 • Scr-1.154 • age-0.203 • (0.742 if female)
• 20. Treatment with chronic systemic glucocorticoid therapy (more than 7 consecutive days in 1 month)
• 21. Treatment with anticoagulants
• 22. Any underlying or acute disease requiring regular medication which could possibly pose a threat to the subject or make implementation of the protocol or interpretation of the study results difficult
• 23. History of alcohol abuse (\>14 per week for men and \>7 per week for women) or illicit drug use
• 24. Treatment with any investigational drug in the one month preceding the study
• 25. Previous randomization in this trial
• 26. Mental conditions rendering a subject unable to understand the nature, scope and possible consequences of the study
• 27. Inability to comply with the protocol in the opinion of the principal investigator, e.g., uncooperative attitude, inability to return for follow-up visits, and unlikelihood of completing the study
• 28. Uncircumcised men or men with history of balanitis
• 29. History of urinary incontinence
• 30. History of recurrent (\>3) episodes of vulvovaginitis per year, or severe symptoms
• 31. History of Fournier's gangrene
• 32. History of recurrent (≥3) UTIs per year or pyelonephritis
• 33. History of symptomatic hypotension or conditions predisposing to volume depletion
• 34. Known peripheral vascular disease, neuropathy, history of foot ulcers or lower limb amputations
• 35. Treatment with loop diuretics furosemide, torsemide, bumetanide, ethacrynic acid
• 36. Known or suspected allergy to trial medications, excipients, or related products
• 37. Contraindications to study medications, worded specifically as stated in the product's prescribing information