Effects of Sodium-glucose Co-transporter-2( SGLT-2 ) Inhibition on Sympathetic Nervous System Activity in Humans

Effects of SGLT-2 Inhibition on Sympathetic Nervous System Activity in Humans

This study is designed to investigate whether the sodium-glucose co-transporter-2 (SGLT-2) inhibitor Empagliflozin reduces sympathetic nervous system (SNS) activity in humans.

This is a randomised, double-blind, placebo controlled, cross-over study. Participants will be randomly assigned to receive either Empagliflozin 10mg/daily or Placebo and will later receive the alternate treatment.

Comprehensive testing will occur after each 4 week treatment phase and will include assessment of muscle sympathetic nerve activity, cardiac and renal noradrenaline spillover to assess organ specific SNS activity.

Inclusion Criteria:

• Age: 25 -65 years
• (Body Mass Index) BMI≥30kg/m2
• Currently weight stable (+/- 3% in previous 6-12 months and not on any specific exercise or dietary program)
• Metabolic syndrome (defined as having: obesity (BMI ≥30kg/m2 ) plus any two of the following four factors: Elevated triglycerides (Triglyceride≥ 1.7mmol/L), Reduced HDL (High - density lipoprotein) cholesterol (<1.0mmol/L in males, <1.3mmol/L in females), Elevated clinic systolic (Blood Pressure) BP ≥130 or diastolic BP ≥85mmHg, Fasting glucose ≥5.6mmol/L or type 2 diabetes.
• office BP for screening purposes ≤160/90mmHg
• drug naïve for at least 6 weeks prior to baseline assessment

Exclusion Criteria:

• Grade 2-3 hypertension (systolic office BP >160, diastolic office BP >100 mmHg)
• Secondary causes of hypertension
• CKD (Chronic kidney disease) stage 4-5 {(estimated glomerular filtration) eGFR<30ml/min}
• Heart failure NYHA (New York Heart Association) class II-IV
• Recent CV (cardiovascular) event (acute myocardial infarction, acute coronary syndrome, stroke or transient ischaemic attack within the previous six months)
• unstable psychiatric condition
• medication such as corticosteroids, several antidepressants and antipsychotics
• Female participants of childbearing potential must have a negative pregnancy test prior to treatment