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Clinical trial Recruiting at 1 site Early Phase 1 Interventional Ages 30 to 75

How empagliflozin affects liver glucose production, fat breakdown, and nerve-related signals

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

Run by The University of Texas Health Science Center at San Antonio · NCT07053293 · Data updated 2026-11-12

This test will see if the diabetes pill empagliflozin raises liver glucose production, fat breakdown, and ketones in people with type 2 diabetes and whether adding medicines such as propranolol or pioglitazone can block those changes.

More Type 2 Diabetes trials

Quick facts

PhaseEarly Phase 1
Study typeInterventional
Ages30 Years to 75 Years
SexAll
Enrollment22 (estimated)
SponsorThe University of Texas Health Science Center at San Antonio
Academic / other
Locations1 site (San Antonio, Texas)
StatusRecruiting
StartedJanuary 7, 2025
Main results expectedJune 1, 2027
Study endsJune 30, 2027
Registry record updatedJuly 17, 2026
Trial IDNCT07053293 on ClinicalTrials.gov

Is this trial a fit for you?

Likely a good fit

Ideal candidates are adults age 30–75 with type 2 diabetes, BMI 21–45 kg/m2, HbA1c 7.0–11%, eGFR >60 ml/min/1.73 m2, stable weight, and currently treated with diet, sulfonylurea, metformin, or both.

Probably not a fit

People treated with GLP-1 receptor agonists, DPP-4 inhibitors, thiazolidinediones, or insulin, or those with eGFR ≤60 ml/min/1.73 m2, uncontrolled blood pressure, or outside the age/BMI ranges are unlikely to qualify or benefit from participation.

A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.

What this trial studies

This is a mechanistic, randomized early-phase study in about 20–22 people with type 2 diabetes using intensive tracer infusions to track liver glucose production, lipolysis, ketone production, and whole-body norepinephrine turnover. Participants receive empagliflozin 25 mg and undergo paired study visits in random order with detailed metabolic measurements before and after dosing. Tracers include 6,6-D2-glucose for endogenous glucose production, U-2H-glycerol (or U-14C-glycerol) for lipolysis, 13C-palmitate for ketogenesis, D2O for gluconeogenesis and de novo lipogenesis, and 3H-norepinephrine for sympathetic turnover. The protocol compares empagliflozin alone versus empagliflozin plus interventions (e.g., propranolol or pioglitazone) to separate mechanisms driving ketone and glucose changes.

Why it matters

Potential benefit: If successful, the findings could help clinicians prevent or reduce unwanted increases in ketones, lipolysis, or hepatic glucose output when using SGLT2 inhibitors.

How similar studies have gone: Previous studies have shown SGLT2 inhibitors can increase ketone production and alter glucose handling, but using beta-blockade or TZD co-treatment to separate sympathetic versus adipose-driven mechanisms is relatively novel and incompletely tested.

Who can join: the full rules

Show full inclusion / exclusion criteria 
Patients with T2D

Inclusion Criteria:

* 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.

EXCLUSION CRITERIA

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.

Where it's running

  • Texas Diabetes Institute/UH
    San Antonio, Texas, United States     Recruiting

Study contacts

  • Principal investigator: Ralph DeFronzo, MD — The University of Texas Health Science Center at San Antonio
  • Study coordinator: Ralph DeFronzo, MD
  • Email: defronzo@uthscsa.edu
  • Phone: 210-567-6691

Similar studies

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How to take part

  1. Review the eligibility criteria above with your treating physician.
  2. Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
  3. Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.
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Last reviewed 2026-11-14 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.