Mechanisms of SGLT2 Inhibition in Pediatric Steatotic Liver Disease

Exclusion Criteria37

• ALT > 250U/L at screening
• History of significant alcohol intake or current use
• Impaired fasting glucose (>100 mg/dL)
• Diabetes (type 1 or 2)
• Current or recent (<6 months prior to enrollment) use of weight loss medication(s)
• Vitamin E supplementation or use of metformin
• washout period 30 days
• Previous bariatric surgery
• Prior use of empagliflozin
• Lower limb infection/ulceration within 3 months of screening
• Metal or magnetic implants, devices or objects inside of or on the body, which are not MRI compatible
• Structural and functional urogenital abnormalities, that predispose for urogenital infections
• Recent initiation (<3 months prior to enrollment) of anti-hypertensive or lipid medication(s)
• Major psychiatric disorder
• Known hypothalamic or pituitary dysfunction
• Current pregnancy or plans to become pregnant
• Females unwilling to be tested for pregnancy
• Females who are sexually active and not protects by an effective method of birth control (e.g. UID or medication or patch)
• can re-screen 30 days after getting on birth control
• Tobacco use
• Significant liver dysfunction (levels >5 times the upper limit of normal (ULN)):
• ALT (ULN = 50 U/L)
• AST (ULN = 48 U/L)
• GGT (ULN = 48 U/L)
• ALP (ULN = 115 U/L)
• Platelets < 150,000 cells/mm3
• Total bilirubin > 1.3 mg/dL
• INR > 1.3
• Albumin <3.2 g/dL
• Gilbert's Syndrome
• Any known causes of liver disease (except NAFLD and NASH)
• Significant renal dysfunction (estimated glomerular filtration rate \[eGFR\] < 80 mL/min/1.73 m2),
• Diagnosed monogenic obesity
• History of cancer
• Untreated thyroid disorder
• History of decompensation events (ascites, variceal bleeding, hepatic encephalopathy, or hepatocellular carcinoma)
• Current or recent (<6 months prior to enrollment) use of medication(s) associated with weight gain (e.g. atypical anti-psychotics).