Prevention of Progression of Prediabetes, Obesity and CV Risk (Pre-DM)

Pioneering and Affordable Strategies to Prevent Progression of Prediabetes, Obesity and CV Risk in Hispanics

The investigators are studying how to help people with prediabetes (Pre-DM) and obesity. The goal is to use new and affordable treatments to bring blood sugar levels back to normal and help participants to lose weight. The investigators also want to reduce participants risk of heart problems. The study team will look at how these treatments affect metabolism and other body functions to help find new ways to treat diabetes and obesity in the future.

Study Overview

• Status: Recruiting
• Conditions: Cardiovascular Diseases; Weight, Body; Pre-Diabetes
• Intervention / Treatment: Drug: Placebo; Drug: Jardiance 25Mg Tablet; Drug: Rybelsus Tablet; Drug: Metformin; Drug: Actos

Detailed Description

While taking part in this study, participants will be asked to attend approximately 16 visits with the researchers or study staff.

Study participants are assigned (single-blinded, only the study team will know the assigned group) to one of 4 study groups, receiving a 6-month treatment with Nutritional Consultation + either SGLT2 Inhibitor (Empagliflozin), Rybelsus (GLP1 Receptor Agonist), Metformin + Pioglitazone, or placebo. A placebo is an inactive, harmless substance that looks like the other study drugs. This study does not require overnight stays at the hospital in any of the study groups.

Duration of the Study will be about 6-7 months.

• Study Type: Interventional
• Enrollment (Estimated): 64
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Carolina Solis-Herrera, MD; Phone Number: 210-567-4900; Email: solisherrera@uthscsa.edu
• Study Contact Backup: Name: Francisca Acosta, PhD; Email: acostafm@uthscsa.edu

Study Locations

• United States
  • Texas
    • San Antonio, Texas, United States, 78229
      • Recruiting
      • University of Texas Health Science Center at San Antonio
      • Contact: Carolina Solis-Herrera, MD; Phone Number: 210-567-4900; Email: solisherrera@uthscsa.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Patients will have an established diagnosis of pre-Diabetes Mellitus (DM) before the screening visit, documented by an acceptable modality in the last 6 months.
2. Age ≥ 18 years old
3. Body Mass Index (BMI)=25-40 kg/m2
4. Glycated Hemoglobin (HbA1c) = 5.7-6.4%
5. Blood Pressure (BP) <160/100
6. Estimated Glomerular Filtration Rate (eGFR) ≥30 ml/min•1.73m2
7. Body weight must be stable (±5 pounds) over the last 3 months.
8. Oral diuretics, if prescribed to the patient according to local guidelines and discretion of the investigator, should be stable for at least 1 week prior to randomization.
9. Hispanic ethic group
10. Willing to adhere to medication regimen for up to 6 months.

11. Male or female, if female, met these criteria:

    1. Not pregnant or breast-feeding
    2. Negative pregnancy test result at visit 1 (screening)
    3. During the entire study, women of childbearing potential (WOCBP) including peri-menopausal women who have a menstrual period within 1 year must practice appropriate, and effective birth control, either implants or pills, or a vasectomized partner prior to receiving the first dose of study medication
12. Does not suffer from severe claustrophobia
13. No contraindication for Magnetic Resonance Imaging (MRI) (metal plates, screws, shrapnel, pins, or cardiac pacemaker)

Exclusion Criteria:

1. Patients currently on one of the selected therapies
2. Extended diagnoses with Type 2 Diabetes
3. Pregnancy, lactation, women of childbearing age (WOCBA) unwilling to use contraception
4. Known allergy/sensitivity to study drugs or their ingredients
5. Major oncologic diagnosis in the last 5 years
6. Current drug or alcohol use or dependence that, in the opinion of the site investigator, would interfere with adherence to study requirements
7. Inability or unwillingness of individual or legal guardian/representative to give written informed consent
8. Major organ or metabolic diseases, or physical limitations that will not allow the subject to complete the study
9. Myocardial infraction, coronary artery bypass graft surgery, or other major cardiovascular event in the past 60 days
10. Heart transplant recipient or listed for a heart transplant
11. Currently implanted left ventricular assist device
12. Cardiomyopathy based on infiltrative or cumulative hypertrophic obstructive cardiomyopathy or known pericardial constriction
13. Any severe (obstructive or regurgitant) valvular heart disease, expected to lead to surgery during the trial period
14. Acute decompensated heart failure requiring intravenous diuretics, vasodilators, inotropic agents, or mechanical support within 1 week of screening and during the screening period prior to randomization
15. Implanted cardioverter defibrillator within 3 months prior to screening
16. Cardiac resynchronization therapy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Randomization will occur 1:1:1:1 to this placebo group	Drug: Placebo; Oral tablet administered once daily; Other Names: Zebbo
Experimental: SGLT2 inhibitor Group; Randomization will occur 1:1:1:1 to this SGLT2 inhibitor group	Drug: Jardiance 25Mg Tablet; Oral 25 mg Sodium-Glucose Co-Transporter (SGLT2) inhibitor administered once daily; Other Names: Empagliflozin
Experimental: GLP-1 Receptor Agonist Group; Randomization will occur 1:1:1:1 to this GLP-1 receptor agonist group	Drug: Rybelsus Tablet; Oral tablet started at a 3mg dose once daily and increased to 7mg once daily or maximum tolerable dose.; Other Names: Semaglutide
Experimental: Metformin with SGLT2 Inhibitor Group; Randomization will occur 1:1:1:1 to this metformin plus SGLT2 inhibitor group	Drug: Metformin; Oral tablet started at a dose of 500mg with an increase of 500mg weekly up to a maximum dose of 2000mg (4 tablets); Other Names: Metformin Hydrochloride; Drug: Actos; Oral tablet dosed at 15mg once daily; Other Names: Pioglitazone

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hemoglobin A1c Level (HBA1c)	Percentage of glycated hemoglobin level in blood	Baseline and 6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Body Mass Index (BMI)	Measure of body fat based on height and weight that applies to adult men and women	Baseline and 6 months
Percentage of Body Fat Composition	Measurement of body fat using a DEXA scan	Baseline and 6 months
Left Ventricular Function	Cardiac function is measured by left-ventricular function measured using cardiac MRI and expressed as a percentage	Baseline and 6 months
Measure of phosphocreatine k-value	A skeletal muscle bioenergetic measurement using skeletal muscle MRI/MRS	Baseline and 6 months
Measure of oxidative capacity	A skeletal muscle bioenergetic measurement using skeletal muscle MRI/MRS	Baseline and 6 months
Measure of intramyocellular lipids (IMCL)	A skeletal muscle bioenergetic measurement using skeletal muscle MRI/MRS	Baseline and 6 months
Measure of extramyocellular lipids (EMCL)	A skeletal muscle bioenergetic measurement using skeletal muscle MRI/MRS	Baseline and 6 months
Patient Reported Outcomes (PROMIS)	A survey used to assess physical function. Subjects will rank 20 questions from a scale of 1 - 5, with 5 being the highest physical function and 1 being the lowest. The score will be added up, and the Raw score will be converted to T-Score using the PROMIS Adult v2.0 Physical Function 20a Short Form Conversion Table. The range of T-scores is 12.1-62.5. A higher score indicates higher physical function.	Baseline and 6 months

Collaborators and Investigators

• Sponsor: The University of Texas Health Science Center at San Antonio
• Collaborators: Baptist Health Foundation of San Antonio
• Investigators: Principal Investigator: Carolina Solis-Herrera, MD, The University of Texas Health Science Center at San Antonio

Study record dates

Study Major Dates

• Study Start (Actual): September 11, 2024
• Primary Completion (Estimated): July 1, 2027
• Study Completion (Estimated): July 1, 2027

Study Registration Dates

• First Submitted: May 31, 2024
• First Submitted That Met QC Criteria: May 31, 2024
• First Posted (Actual): June 6, 2024

Study Record Updates

• Last Update Posted (Actual): November 12, 2025
• Last Update Submitted That Met QC Criteria: November 10, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Keywords: Hispanic; Prevention of progression; Affordable strategies
• Additional Relevant MeSH Terms: Metabolic Diseases; Glucose Metabolism Disorders; Hyperglycemia; Pathological Conditions, Signs and Symptoms; Nutritional and Metabolic Diseases; Signs and Symptoms; Cardiovascular Diseases; Body Weight; Glucose Intolerance; Sulfur Compounds; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pharmaceutical Preparations; Dosage Forms; Thiazoles; Azoles; Biguanides; Guanidines; Amidines; Thiazolidinediones; Pioglitazone; Metformin; semaglutide; empagliflozin; Tablets
• Other Study ID Numbers: STUDY00000485 Pre-DM

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The Institution or respective designees may present or publish the results of a scientific investigation involving this Study in accordance with International Committee of Medical Journal Editors (ICMJE). The Sponsor Investigator, funding agency, or PI initiating the study will collaborate to determine who has publication rights for authorship upon review and approval of proposed manuscripts.
• IPD Sharing Time Frame: At the time of publication in a peer review journal
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No