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

The Deutsche Diabetes Forschungsgesellschaft e.V.

Status and phase

Completed

Phase 4

Conditions

Non-alcoholic Fatty Liver Disease

Type 2 Diabetes

Treatments

Drug: Empagliflozin

Drug: Placebo

Study type

Interventional

Funder types

Other

Industry

Identifiers

NCT02637973

EmLiFa001

Details and patient eligibility

About

The effects of empagliflozin treatment on hepatocellular lipid content, liver energy metabolism and body composition will be investigated in a multicentre, prospective, placebo-controlled, double-blind, randomized, 2-arm parallel, interventional and exploratory pilot study in patients with newly diagnosed type 2 diabetes.

Full description

In this multicentre, prospective, placebo-controlled, double-blind, randomized, 2-arm parallel, interventional pilot study HCL and intramyocellular lipids (IMCL) will be quantified with 1H magnetic resonance (MR) spectroscopy. Hepatic ATP and inorganic phosphate (Pi) concentrations will be assessed with 31P MR spectroscopy (1). Whole-body and hepatic insulin sensitivity and metabolic flexibility will be measured by combining hyperinsulinemic-euglycemic pancreatic clamp tests with isotopic dilution of 6,6-2H2 glucose and indirect calorimetry as shown (2). Abdominal fat distribution will be quantified by MR imaging.

Newly diagnosed patients with type 2 diabetes (T2D) will be randomly allocated to once daily 25 mg empagliflozin (EMPA) or placebo for 24 weeks with a computer-generated random sequence and will be masked to the treatment assignment. Participants will visit the clinical research center at baseline, 12 weeks and 24 weeks for MRS and metabolic examinations, including blood sampling for hepato- and adipocytokines. Anthropometric parameters (body weight, waist circumference, total body fat, blood pressure) and glycemic control (HbA1C, fasting blood glucose, FBG) will be assessed at baseline and during monitoring visits every 4 weeks.

Enrollment

84 patients

Sex

All

Ages

18 to 75 years old

Volunteers

No Healthy Volunteers

Inclusion criteria

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