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

Empagliflozin effects on ketone production, liver glucose output, and fluid balance in type 2 diabetes

Official title: Protocol III: SGLT2i, Ketoacidosis, Volume Contraction, and Insulinopenia

Run by The University of Texas Health Science Center at San Antonio · NCT07053306 · Data updated 2026-11-12

This trial will test whether taking empagliflozin makes the liver produce more glucose and the body break down fat and make ketones in people with type 2 diabetes when mild volume loss combines with lower insulin levels.

More Type 2 Diabetes trials

Quick facts

PhasePhase 1
Study typeInterventional
Ages30 Years to 75 Years
SexAll
Enrollment29 (estimated)
SponsorThe University of Texas Health Science Center at San Antonio
Academic / other
Locations1 site (San Antonio, Texas)
StatusRecruiting
StartedApril 29, 2025
Main results expectedJune 1, 2027
Study endsJune 30, 2027
Registry record updatedJuly 17, 2026
Trial IDNCT07053306 on ClinicalTrials.gov

Is this trial a fit for you?

Likely a good fit

Adults 30–75 years old with type 2 diabetes, HbA1c 7–11%, BMI 21–45 kg/m2, eGFR >60 ml/min/1.73m2, stable weight, and treated with diet, metformin and/or sulfonylurea are ideal candidates.

Probably not a fit

People using insulin, GLP‑1 receptor agonists, DPP‑4 inhibitors, or TZDs, those with reduced kidney function, unstable medical conditions, or who fall outside the listed age/BMI/HbA1c ranges are unlikely to be eligible or to 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 Phase 1 interventional protocol gives a single 25 mg dose of empagliflozin during controlled metabolic visits using pancreatic clamp techniques and stable isotope tracer infusions to measure hepatic glucose production, lipolysis, and ketogenesis. Participants complete multiple randomized early-morning visits at the Clinical Research Center with continuous glucose and glycerol tracers and frequent blood sampling over about eight hours. The protocol compares responses under experimental conditions that mimic mild volume depletion and insulinopenia to test whether both changes are required for SGLT2 inhibitor–related rises in endogenous glucose production and ketone formation. Eligible participants are adults with type 2 diabetes (ages 30–75) meeting prespecified HbA1c, BMI, renal function, and medication criteria and not using insulin or several other diabetes drug classes.

Why it matters

Potential benefit: If successful, this work could clarify why some people on SGLT2 inhibitors develop ketone-related complications and help clinicians reduce that risk through better patient selection and monitoring.

How similar studies have gone: Previous clinical and mechanistic studies show SGLT2 inhibitors raise circulating ketones and can increase endogenous glucose production, but the specific hypothesis that volume depletion plus insulinopenia together cause those changes is novel and not fully tested in humans.

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.
* Statin therapy is permissible if the dose has been stable for at least 3 months

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.