Study Design

All studies will be performed on the CRC at the Texas Diabetes Institute at 6:00 A.M. after 10-h overnight fast except water. After confirming eligibility, subjects will be randomized to receive empagliflozin (n=20) or placebo (n=10) in 2:1 ratio. Subject stratification will be done according to the following parameters: age (> or < 50 y), BMI (> or < 30 kg/m2), eGFR (> or < 80 ml/min/1.73 m2), HbA1c (> or < 8.5%). Each subject will participate in two studies performed in random order with 10-21 day interval between studies. Background medications (metformin, or MET, and/or sulfonylurea, or SU) will be withheld on the morning of study.   In Study 1, EGP will be measured with a prime-continuous 6,6, D2-glucose infusion and lipolysis will be measured with prime-continuous infusion of U-2H-glycerol.  The rate of ketogenesis will be determined by infusion of 13C palmitate and quantitating the enrichment of 13C in 3-hydroxybutyrate (b-OHB).  Total body NE turnover will be measured with 3H-norepinephrine (3H-NE) infusion before and after empagliflozin administration.  Study 2 will be similar to Study 1 with one exception.  EGP, lipolysis, and ketogenesis, and NE turnover will be measured under pancreatic clamp conditions.