SGLT2i, Hepatic Glucose Production, and SNS

NCT07053293 | Recruiting Early Phase 1 DMC FDA Drug

• 2 other identifiers: 20230457HU - 504075R01DK024092
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Type 2 Diabetes

Keywords

Endogenous glucose production; Ketogenesis; Gluconeogenesis; Lipolysis; Norepinephrine turnover

Outcome Measures

Primary Outcomes (1)

• Endogenous Glucose Production (EGP)

  Measurement of Endogenous Glucose Production (EGP) using stable isotope (6,6, D2- glucose infusion).

  0 and 300 minutes

Study Arms (1)

Empagliflozin

EXPERIMENTAL

Empagliflozin 25 mg/day

Drug: Empagliflozin 25 MG

Interventions

Empagliflozin 25 MG DRUG

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.

Also known as: Jardiance

Empagliflozin

Eligibility Criteria

• Age: 30 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• The University of Texas Health Science Center at San Antonio: lead
• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): collaborator

Study Sites (1)

Texas Diabetes Institute/UH

San Antonio, Texas, 78229-3900, United States

RECRUITING

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Interventions

empagliflozin

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Study Officials

• Ralph DeFronzo, MD

  University of Texas Health Science Center San Antonio

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Ralph DeFronzo, MD

CONTACT

210-567-6691; defronzo@uthscsa.edu

Aurora Merovci, MD

CONTACT

210-567-6691; merovci@uthscsa.edu

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Masking Details: None (Open Label)
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: A clinical trial comprised of 2 studies

Study Record Dates

• First Submitted: June 26, 2025
• First Posted: July 8, 2025
• Study Start: January 7, 2025
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): June 30, 2027
• Last Updated: July 11, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: At study end after analysis of data.

Locations

US (1)