SGLTi, Hepatic Glucose Production and Ketogenesis
Trial Parameters
Brief Summary
In this study, we will test the hypothesis that distinct mechanisms account for the SGLT2i-induced stimulation of ketogenesis and lipolysis versus endogenous (hepatic) glucose production in patients with type 2 diabetes (T2D) and type 1 diabetes (T1D), and that the increases in ketone production and lipolysis can be prevented by concomitant administration of the thiazolidinedione pioglitazone. We will conduct five distinct experiments to test this hypothesis in patients with T2D and T1D. MAIN STUDY: To examine the effect of empagliflozin versus empagliflozin/pancreatic clamp on EGP (6,6, D2-glucose), gluconeogenesis (D2O), lipolysis (U-2H-glycerol), ketogenesis (13C-palmitate conversion to 3-betahydroxybuyrate), and norepinephrine turnover (3H-NE) in type 2 diabetes subjects.
Eligibility Criteria
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) \< 160/90 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 treated with diet, sulfonylurea (SU), metformin (MET), or SU/MET * Statin therapy is permissible if the dose has been stable for at least 3 months Exclusion Criteria: * Patients treated with Glucagon-like peptide 1 receptor agonists (GLP-1 RA), Dipeptidyl Peptidase IV inhibitors (DPP-4i), Thiazolidinediones (TZD), or insulin are excluded * Patients taking medications (other than SU/MET) known to aff