NCT05960656

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.

Trial Health

77
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
30

participants targeted

Target at P25-P50 for phase_1 type-2-diabetes

Timeline
13mo left

Started Oct 2023

Longer than P75 for phase_1 type-2-diabetes

Geographic Reach
1 country

1 active site

Status
recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress69%
Oct 2023Jun 2027

First Submitted

Initial submission to the registry

July 13, 2023

Completed
14 days until next milestone

First Posted

Study publicly available on registry

July 27, 2023

Completed
2 months until next milestone

Study Start

First participant enrolled

October 5, 2023

Completed
3.7 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

June 1, 2027

Expected
29 days until next milestone

Study Completion

Last participant's last visit for all outcomes

June 30, 2027

Last Updated

July 1, 2025

Status Verified

June 1, 2025

Enrollment Period

3.7 years

First QC Date

July 13, 2023

Last Update Submit

June 26, 2025

Conditions

Type 2 Diabetes

Keywords

Pancreatic clampEndogenous glucose productionKetogenesisGluconeogenesisLipolysisNorepinephrine 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 (2)

Empagliflozin

EXPERIMENTAL

Empagliflozin 25 mg/day

Drug: Empagliflozin 25 MG

Placebo/Control Group

PLACEBO COMPARATOR

Placebo control

Other: Placebo

Interventions

Empagliflozin 25 MGDRUG

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
PlaceboOTHER

Inert tablet

Also known as: Placebo for empagliflozin
Placebo/Control Group

Eligibility Criteria

Age30 Years - 75 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

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 MellitusGlucose Metabolism DisordersMetabolic DiseasesNutritional and Metabolic DiseasesEndocrine System Diseases

Study Officials

  • Ralph DeFronzo, MD

    University of Texas Health Science Center San Antonio

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Ralph DeFronzo, MD

CONTACT

210-567-6691defronzo@uthscsa.edu

Aurora Merovci, MD

CONTACT

210-567-6691merovci@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 2:1 active drug:placebo.
Purpose
BASIC SCIENCE
Intervention Model
PARALLEL
Model Details: A randomized controlled 2 arm clinical trial
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

July 13, 2023

First Posted

July 27, 2023

Study Start

October 5, 2023

Primary Completion (Estimated)

June 1, 2027

Study Completion (Estimated)

June 30, 2027

Last Updated

July 1, 2025

Record last verified: 2025-06

Data Sharing

IPD Sharing
Will share

Deidentified data will be shared with NIH and as a publication in a peer reviewed journal once data are published.

Shared Documents
STUDY PROTOCOL, SAP, ICF
Time Frame
At study end after analysis of data.

Locations

US(1)