RecruitingEarly Phase 1NCT07053293

SGLT2i, Hepatic Glucose Production, and SNS

Protocol II: SGLT2i, Hepatic Glucose Production, and Sympathetic Nervous System (SNS)

Sponsor

The University of Texas Health Science Center at San Antonio

Enrollment

22 participants

Start Date

Jan 7, 2025

Study Type

INTERVENTIONAL

Conditions

Type 2 Diabetes

Summary

In this study, PI 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) that the increases in ketone production and lipolysis can be prevented by concomitant administration of the thiazolidinedione pioglitazone. Principal Investigator (PI) will conduct five distinct experiments to test this hypothesis in patients with T2D. To examine the role of the SNS on the empagliflozin-induced stimulation of EGP, lipolysis, and ketone production in T2D by comparing the effect of empagliflozin versus empagliflozin plus propranolol.

Eligibility

Min Age: 30 YearsMax Age: 75 Years

Inclusion Criteria10

Patients with T2D
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 Criteria4

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 affect glucose metabolism are excluded
Subjects with evidence of proliferative retinopathy or eGFR \< 60 are excluded
Women of childbearing potential are excluded unless they are taking/using appropriate contractive medications/devices

Interventions

DRUGEmpagliflozin 25 MG

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.