Protocol lV: SGLT2 Inhibitors, Pioglitazone and Ketone Production in Type 2 Diabetes Mellitus
The University of Texas Health Science Center at San Antonio
Summary
To examine whether the empagliflozin-induced stimulation of EGP, lipolysis, and ketone production in T2D individuals can be blocked by pioglitazone (which has direct hepatic and adipose tissue effects).
Description
Participants: 64 T2D subjects with the same inclusion and exclusion criteria as Protocol 1. Subjects with hematuria are excluded. Study Design: Infusions of 3-3H-glucose and 14C-glycerol are started and continued to study end (2 PM). Baseline blood samples for HbA1c (x2) and for plasma insulin, glucagon, glucose, FFA, BHB, AcAc, glycerol, and plasma 3-3H-glucose and 14C-glycerol specific activities are drawn at -30, -20, -10, -5, and 0 minutes for measurement of lipolysis, ketone production (plasma ketone levels), and EGP. Empagliflozin (25 mg) is ingested at time zero (9AM) and plasma sample…
Eligibility
- Age range
- 30–75 years
- Sex
- All
- Healthy volunteers
- No
Patients with T2D Inclusion Criteria: * Ages 30-75 years * Body Mass Index (BMI) 21-45 kg/m2 * Hemoglobin A1C (HbA1c) = 7.0-11% * Estimated glomerular filtration rate (eGFR) \> 60 ml/min/1.73m2 * Blood Pressure (BP) \< 145/85 mmHg * Participants must be in general good health based on medical history, physical exam, screening blood chemistries, complete blood chemistry (CBC), thyroid stimulating hormone/thyroxine (TSH/T4), electrocardiogram (EKG), and urinalysis * Stable body weight (±1.5 kg) over the last 3 months and must not participate in an excessively heavy exercise program * Patients…
Interventions
- DrugEmpagliflozin 25 MG plus Pioglitazone placebo
A medication used in the management and treatment of type 2 diabetes mellitus. It is in the sodium-glucose co-transporter (SGLT-2) class of medications.
- DrugPioglitazone 15 mg increased to 30 mg after 2 weeks plus Empagliflozin Placebo
Placebo-Inert tablet
- DrugEmpagliflozin 25 mg/d plus Pioglitazone (15/30 mg/d)
Pioglitazone, a medication used in the management and treatment of type 2 diabetes mellitus. It is in the thiazolidinedione class of medications
- DrugPioglitazone placebo + Empagliflozin placebo
Placebo-Inert tablet
Location
- Texas Diabetes Institute/UHSan Antonio, Texas