SGLT-2 inhibitors belong to a new class of hypoglycemic drugs with the unique property of decreasing blood glucose through an increase in glucosuria. These drugs inhibit the sodium glucose transporter 2 (SGLT2) expressed at the luminal membrane of the proximal tubule.

SGLT-2 inhibition in type 2 diabetic subjects and in healthy volunteers shifts the threshold for renal glucose excretion to lower levels. This effect is independent from insulin. The inhibition of SGLT2 decreases HbA1C, systolic blood pressure and weight in diabetic subjects. Recently, the EMPA-REG trial demonstrated a decrease in cardiovascular mortality and renal endpoints in empagliflozin treated type 2 diabetic patients with established cardio-vascular disease.

Because this novel hypoglycemic drug has unique and direct effects on renal tissue metabolism, it is important to better examine its effects on the kidney. With this study, we propose to explore the effects of empagliflozin on renal tissue oxygenation. Our hypothesis is that SGLT-2 inhibition decreases renal cortical energy requirements with consequently an increase in renal tissue oxygenation.

This study is a double-blind, randomized, placebo-controlled study that will examine the acute and chronic renal effects of empagliflozin in healthy volunteers.

A total of 45 healthy volunteers will be included in the study: 15 normal weight, 15 overweight (BMI: 25-30kg/m2) and 15 obese (BMI>30kg/m2) non diabetic subjects (as determined after an oral glucose tolerance test).

Empagliflozin 10mg vs placebo will be administered in a blinded fashion qd. The acute and chronic renal response to empagliflozin will be assessed.

Inclusion Criteria:

• Normal weight (BMI: 19-24.9kg/m2), overweight (BMI:25-30kg/m2) or obesity (BMI>30kg/m2)
• Men and women (with a negative pregnancy test) during the follicular phase of the menstrual cycle. All groups will have a balanced number of men and women.
• OGTT/HbA1C: normal or pre-diabetes
• eGFR>60ml/min, albumin/creatinine ratio <3.3mg/mmol (<30 mg/g)
• Signed consent form
• Normal renal ultrasound
• Normal urine dipstick

Exclusion Criteria:

• Antihypertensive therapy
• NSAID treatment
• Former bariatric surgery
• Age<18y or >50y
• At risk of dehydration or hypotension
• Past history of recurrent genital or urinary tract infections
• Contra-indication for MR imaging (pacemaker or other implanted metallic device, claustrophobia)
• Pregnancy
• Sustained systolic blood pressure >150mmHg or diastolic blood pressure >95mmHg

Placebo and Empagliflozin pills