SGLTi, Hepatic Glucose Production and Ketogenesis

NCT05960656 | Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: HSC20230457H - 440509R01DK024092
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

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.

Conditions

Type 2 Diabetes

Keywords

Pancreatic clamp; 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 (2)

Empagliflozin

EXPERIMENTAL

Empagliflozin 25 mg/day

Drug: Empagliflozin 25 MG

Placebo/Control Group

PLACEBO COMPARATOR

Placebo control

Other: Placebo

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

Placebo OTHER

Inert tablet

Also known as: Placebo for empagliflozin

Placebo/Control Group

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
• BMI (Body Mass Index) 21-45 kg/m2
• HbA1c = 7.0-11%
• eGFR (estimated glomerular filtration rate)\> 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, CBC (Complete Blood Count), TSH/T4 (thyroid/thyroxine hormone), EKG (electrocardiogram), and urinalysis (UA)
• 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, Sulfonylureas, Metformin, or Sulfonylureas/Metformin (Sulfo/MET)
• Participants receiving a Glucagon like peptide -1 receptor agonist (GLP1-RA) must be on a stable dose for at least three months prior to study enrollment.
• Participants receiving a Dipeptidyl peptidase 4 inhibitors (DPP-4 inhibitor) must be on a stable dose for at least two months prior to study enrollment.
• SGLT2 inhibitors must be discontinued at least two months prior to study enrollment.
• Statin therapy is permissible if the dose has been stable for at least 3 months

You may not qualify if:

• An individual who meets any of the following criteria will be excluded from participation in this study:
• Patients treated with Thiazolidinediones (TZDs), or Insulin are excluded.
• Patients taking medications other than Sulfonylureas/Metformin (SU/MET), stable dose of GLP1-RA and DPP4i known to affect glucose metabolism are excluded. Patients taking SGLT2i within 2 months of screening visit will be excluded from participating in this study, however they may be asked whether they would agree to discontinue the medication for two months to become eligible. (Please see clarification below.) \*
• Subjects with evidence of proliferative retinopathy or estimated glomerular filtration rate (eGFR) \< 60 are excluded
• Women of childbearing potential are excluded unless they are taking/using appropriate contractive medications/devices \* Only participants who are taking SGLT2 inhibitors during the prescreening period will be asked to discontinue the medication at least two months prior to the screening visit. If they agree, they will return for an HbA1c measurement four weeks after stopping the SGLT2 inhibitor.
• If their HbA1c rises to greater than 10%, treatment will be initiated with either metformin, a DPP-4 inhibitor, or a sulfonylurea. We do not anticipate any adverse effects during this initial period, provided the HbA1c remains below 10%.
• HbA1c will be measured using a fingerstick test, which requires only a minimal amount of blood. No compensation will be provided during this phase.
• After two months of medication discontinuation, participants will return for a screening visit. If they meet all eligibility criteria, they will be enrolled in the study and payment done by protocol.

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

  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 2:1 active drug:placebo.
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: A randomized controlled 2 arm clinical trial

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 17, 2026

Record last verified: 2026-07

Data Sharing

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

Locations

US (1)