Understanding the mechanisms of how the Type 2 Diabetes medication SGLT2 Inhibitor works on glucose production and induces the breakdown of fatty acids.
Principal Investigator
Ralph DeFronzo
Renata Belfort De Aguiar
210-450-3076
belfortda@uthscsa.edu
Andrea Hansis-Diarte
210-567-3208
hansisdiarte@uthscsa.edu
Aurora Merovci
210-567-6691
merovci@uthscsa.edu
Cynthia Ramirez
210-358-7200
ramirezc8@uthscsa.edu
Type 2 Diabetes between the ages = 30-75 y, BMI = 23-38 kg/m2, HbA1c = 7.0-10%, eGFR > 60 ml/min/1.73m2, BP < 145/85 mmHg. Participants must be in general good health. Patients treated with diet, SU, metformin, or SU/MET
Patients treated with GLP-1 RA, DPP-4i, TZD, or insulin are excluded
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.