How empagliflozin affects liver glucose production, fat breakdown, and nerve-related signals
Protocol II: SGLT2i, Hepatic Glucose Production, and Sympathetic Nervous System (SNS)
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.
Quick facts
| Phase | Early Phase 1 |
|---|---|
| Study type | Interventional |
| Enrollment | 22 (estimated) |
| Ages | 30 Years to 75 Years |
| Sex | All |
| Sponsor | The University of Texas Health Science Center at San Antonio Academic / other |
| Locations | 1 site (San Antonio, Texas) |
| Trial ID | NCT07053293 on ClinicalTrials.gov |
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.
Who should consider this trial
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.
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.
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 performed: 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.
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.