Empagliflozin effects on ketone production, liver glucose output, and fluid balance in type 2 diabetes
Protocol III: SGLT2i, Ketoacidosis, Volume Contraction, and Insulinopenia
PHASE1 · The University of Texas Health Science Center at San Antonio · NCT07053306
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.
Quick facts
| Phase | PHASE1 |
|---|---|
| Study type | Interventional |
| Enrollment | 29 (estimated) |
| Ages | 30 Years to 75 Years |
| Sex | All |
| Sponsor | The University of Texas Health Science Center at San Antonio (other) |
| Locations | 1 site (San Antonio, Texas) |
| Trial ID | NCT07053306 on ClinicalTrials.gov |
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.
Who should consider this trial
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.
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.
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 performed: 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.
Eligibility criteria
Show full inclusion / exclusion criteria
Patients with T2D Inclusion Criteria: * 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 Exclusion Criteria: * 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
Where this trial is running
San Antonio, Texas
- 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
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
Conditions: Type 2 Diabetes, Pancreatic clamp, Endogenous glucose production, Ketogenesis, Gluconeogenesis, Lipolysis