Investigating the effects of SGLT2 inhibitors on ketogenesis and glucose production in diabetes

Protocol l: SGLT2 Inhibitors, Ketogenesis, and Ketoacidosis

Phase 1 Interventional The University of Texas Health Science Center at San Antonio · NCT05960656

This study tests how a diabetes medication called empagliflozin affects fat and sugar production in people with type 1 and type 2 diabetes.

Quick facts

PhasePhase 1
Study typeInterventional
Enrollment30 (estimated)
Ages30 Years to 75 Years
SexAll
SponsorThe University of Texas Health Science Center at San Antonio Academic / other
Locations1 site (San Antonio, Texas)
Trial IDNCT05960656 on ClinicalTrials.gov

What this trial studies

This study aims to explore the mechanisms behind the stimulation of ketogenesis and lipolysis versus endogenous glucose production induced by SGLT2 inhibitors in patients with type 1 and type 2 diabetes. It will involve five distinct experiments, including the administration of empagliflozin and the evaluation of its effects on various metabolic processes. Participants will be randomized to receive either empagliflozin or a placebo, with additional assessments involving the thiazolidinedione pioglitazone. The study will measure key metabolic markers to understand the interactions between these treatments and their effects on glucose metabolism.

Who should consider this trial

Good fit: Ideal candidates for this study are adults aged 30-75 with type 2 diabetes who have stable health and meet specific metabolic criteria.

Not a fit: Patients currently on GLP-1 receptor agonists, DPP-4 inhibitors, thiazolidinediones, or insulin may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could lead to improved treatment strategies for managing diabetes by optimizing the use of SGLT2 inhibitors.

How similar studies have performed: Other studies have shown promising results with SGLT2 inhibitors, but this specific approach to understanding ketogenesis and glucose production is novel.

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

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. 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 DiabetesPancreatic clampEndogenous glucose productionKetogenesisGluconeogenesisLipolysisNorepinephrine turnover
Last reviewed 2026-06-13 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.