SGLT2i, Pioglitazone, and Ketone Production in T2D

NCT07053319 | Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: 20230457HU-504077R01DK024092
• Study Type: interventional
• Target: 64
• Locations: 1 country
• Sites: 1

Brief 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).

Conditions

Type 2 Diabetes

Keywords

Endogenous glucose production; Ketogenesis; Gluconeogenesis; Lipolysis

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 (4)

Empagliflozin plus Pioglitazone placebo

EXPERIMENTAL

Empagliflozin 25 mg/day plus pioglitazone placebo

Drug: Empagliflozin 25 MG plus Pioglitazone placebo

Pioglitazone plus Empagliflozin Placebo

PLACEBO COMPARATOR

Pioglitazone, 15 mg/day, increased to 30 mg after 2 weeks plus empagliflozin placebo

Drug: Pioglitazone 15 mg increased to 30 mg after 2 weeks plus Empagliflozin Placebo

Empagliflozin plus Pioglitazone

EXPERIMENTAL

Empagliflozin(25mg/day) plus pioglitazone (15/30 mg/d)

Drug: Empagliflozin 25 mg/d plus Pioglitazone (15/30 mg/d)

Empagliflozin placebo + pioglitazone placebo

EXPERIMENTAL

empagliflozin placebo plus pioglitazone placebo

Interventions

Pioglitazone 15 mg increased to 30 mg after 2 weeks plus Empagliflozin Placebo DRUG

Placebo-Inert tablet

Also known as: Placebo for empagliflozin, Pioglitazone, a medication used in the management and treatment of type 2 diabetes mellitus. It is in the thiazolidinedione class of medications

Pioglitazone plus Empagliflozin Placebo

Empagliflozin 25 mg/d plus Pioglitazone (15/30 mg/d) DRUG

Pioglitazone, a medication used in the management and treatment of type 2 diabetes mellitus. It is in the thiazolidinedione class of medications

Also known as: Empagliflozin/Pioglitazone, Empagliflozin, 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.

Empagliflozin plus Pioglitazone

Pioglitazone placebo + Empagliflozin placebo DRUG

Placebo-Inert tablet

Also known as: Placebo/Placebo

Empagliflozin 25 MG plus Pioglitazone placebo 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: Empagliflozin, Placebo-Inert tablet

Empagliflozin plus Pioglitazone placebo

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) \< 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 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

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

Study Sites (1)

Texas Diabetes Institute/UH

San Antonio, Texas, 78229-3900, United States

RECRUITING

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Interventions

empagliflozin; Pioglitazone; Sodium-Glucose Transporter 2

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Thiazolidinediones; Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Sodium-Glucose Transport Proteins; Symporters; Ion Pumps; Membrane Transport Proteins; Carrier Proteins; Proteins; Amino Acids, Peptides, and Proteins; Monosaccharide Transport Proteins; Solute Carrier Proteins; Membrane Proteins

Study Officials

• Ralph DeFronzo, MD

  The University of Texas Health Science Center at 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: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: Subjects will be randomly assigned 1:1:1:1 ratio
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: A randomized controlled 4 arm clinical trial

Study Record Dates

• First Submitted: June 26, 2025
• First Posted: July 8, 2025
• Study Start: May 11, 2026
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): June 30, 2027
• Last Updated: May 12, 2026

Record last verified: 2026-03

Data Sharing

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

Locations

US (1)