Effects of Empagliflozin on Liver Fat Content, Energy Metabolism and Body Composition in Patients With Type 2 Diabetes

• age between 18 and 75 years
• BMI\<45 kg/m2
• known diabetes duration up to 7 years
• 6%≤HbA1c≤8%
• drug naïve - no previous antihyperglycemic treatment or one month washout period of treatment with oral glucose lowering drugs (no previous treatment with thiazolidinedione (TZD) drugs allowed)
• obtained written informed consent

Exclusion Criteria:

• uncontrolled hyperglycaemia at screening (glucose level ≥240 mg/dl after an overnight fast, confirmed by a second measurement)
• acute coronary syndrome, stroke or transient ischemic attack within 3 months prior to consent
• previous lower limb amputation
• severe lower limb infection/ulceration within 3 months prior to consent
• liver disease including chronic viral hepatitis (B or C), alcohol abuse, hemochromatosis, alpha-1 antitrypsin deficiency, autoimmune hepatitis, Wilson's disease, primary sclerosing cholangitis or primary biliary cirrhosis, or liver cirrhosis of any etiology
• AST or ALT > 3 x ULN
• positive result on hepatitis B (HBs-AG), hepatitis C (HCV-AB), or HIV 1 and 2 test
• impaired kidney function (estimated glomerular filtration rate [eGFR]\<60 mL/min/1.73m2) during screening
• structural and functional urogenital abnormalities, that predispose for urogenital infections
• gastrointestinal surgeries that induce chronic malabsorption
• history of cancer (except basal cell carcinoma) or treatment for cancer within 5 years
• blood dyscrasias or any disorders causing haemolysis or unstable erythrocytes
• treatment with antiobesity drugs 3 months prior to consent
• treatment with immunomodulatory drugs (oral steroids, antihistamines)
• change in dosage of thyroid hormones within 6 weeks of consent
• pregnancy, lactation period
• metal or magnetic implants, devices or objects inside of or on the body, which are not MRI compatible (according to MRT safety checklist in Appendix 11.3)
• claustrophobia
• cigarette smoking (non-smoker \< 1year), alcohol consumption (male >30 g/d, female >20g/d)
• drug abuse or psychiatric disease
• night-worker or circumstances not allowing normal day-night rhythm
• hypersensitivity to empagliflozin (or drugs of similar chemical structure) or any of the drug compounds
• pharmaceutical preparations with which interactions can be expected - amiloride, furosemide, indapamide, spironolactone, torasemide, triamterene
• use of anti-NASH drugs (vitamin E, ursodeoxycholic acid, S-adenosylmethionine, betaine, silymarin, gemfibrozil, anti-TNF therapies, probiotics) in the 3 months prior to randomization
• women of childbearing potential not using two adequate methods of contraception including a barrier method and a highly efficacious non-barrier method
• persons with any kind of dependency on the investigator or employed by the sponsor or investigator
• persons held in an institution by legal or official order
• participation in another trial in the last 10 weeks before randomization or planned participation during the trial period