Empagliflozin and pioglitazone effects on ketone production in type 2 diabetes

Is this trial a fit for you?

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 Phase 1 study in 64 adults with type 2 diabetes that combines acute tracer-based metabolic testing with a 10-week randomized drug phase. At baseline participants undergo infusion of 3-3H-glucose and 14C-glycerol and serial blood sampling around a single 25 mg dose of empagliflozin to measure endogenous glucose production, lipolysis, and ketone production. Subjects are then randomized to one of four 10-week arms (empagliflozin, pioglitazone, both drugs, or double placebo) with clinic visits every 1–2 weeks for safety and metabolic labs. The baseline metabolic protocol is repeated at week 10 and HbA1c is measured twice during that final week to compare changes across groups.

Why it matters

Who can join: the full rules

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

Other studies for the same condition or treatment. Recruiting studies are listed first.

• Acute Blood Flow Restriction Walking in Type 2 Diabetes

  This study tests whether adding blood flow restriction to treadmill walking affects immune cells in adults with type 2 diabetes.

  Recruiting University of British Columbia · Kelowna, British Columbia · NCT07928531

• Continuous Glucose Monitoring in Type 2 Diabetes Not on Insulin

  This study tests whether using a continuous glucose monitoring system helps people with type 2 diabetes who aren’t using insulin to improve blood sugar control and quality of life.

  Recruiting Medical University of Bialystok · Bialystok · NCT07919236

• Differentiating heart disease in autoimmune vs. type 2 diabetes

  This study tests whether adult-onset autoimmune diabetes (AID/LADA) and type 2 diabetes (T2D) differ in how diabetic heart disease develops, using advanced heart imaging in people with AID, T2D, and healthy controls.

  Recruiting University of Roma La Sapienza · Rome, Roma · NCT07911007

• Lifestyle Metabotype Study B: Understanding Personalized Glucose Responses

  This study tests how lifestyle, metabolism, and brain energy use relate to each person’s blood sugar response after meals, across people with and without prediabetes or type 2 diabetes.

  Recruiting at 2 sites German Institute of Human Nutrition · Berlin and 1 other locations · NCT07888257

• Lifestyle Metabotype Study: How Daily Habits Shape Blood Sugar

  This observational study tests whether personal lifestyle and biological factors can predict how a person’s blood sugar responds after meals.

  Recruiting German Institute of Human Nutrition · Potsdam, Potsdam-Rehbrücke · NCT07868601

• Switching to Zenagamtide From Tirzepatide in Adults With Overweight or Obesity With or Without Type 2 Diabetes

  This study tests whether adults who are overweight or have obesity (with or without type 2 diabetes) can switch from tirzepatide to a new treatment called zenagamtide to find a tolerable dose.

  Recruiting at 2 sites Phase 1 Novo Nordisk A/S · Glendale, California and 1 other locations · NCT07868354

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.