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Diabetes and Vascular Disease

MON-668 - Innovative and Cost-Effective Approaches to Reduce Prediabetes and Cardiovascular Risk Among Hispanics

Monday, June 15, 2026
9:00 AM - 2:00 PM CT
Location: ENDOExpo; Poster Floor
Disclosure(s):
Carolina Solis-Herrera: No relevant disclosure to display


Background: Prediabetes (Pre-DM) is characterized by elevated blood glucose below the diagnostic threshold for type 2 diabetes (T2DM) yet already confers increased risk of microvascular complications, including eye, kidney, and neuropathic disease, as well as cardiovascular (CV) mortality. Pre-DM has reached pandemic proportions, affecting over one-third of U.S. adults, with prevalence projected to approximately double by 2030 and disproportionately burdening Hispanic communities in South Texas.

Objective: To determine the effectiveness of three pharmacologic regimens, combined with standardized nutritional counseling, in reversing Pre-DM to euglycemia and improving metabolic and CV health in Hispanic adults with Pre-DM.

Methods: This is a single-center, single-blind, randomized, placebo-controlled trial enrolling 64 Hispanic adults with Pre-DM (A1c 5.7–6.4%) and BMI 25–40 kg/m² at an academic medical center in San Antonio, Texas. Participants are randomized 1:1:1:1 to receive for six months: (1) placebo, (2) empagliflozin 25 mg daily, (3) semaglutide 7 mg daily or maximum tolerated oral dose, or (4) metformin 2 g plus pioglitazone 15 mg daily; all participants to receive standardized nutritional counseling. The primary endpoint is reversion to euglycemia, defined as A1c ≤ 5.7% at six months. Secondary outcomes include changes in body composition (DXA), cardiac structure and function (cardiac MRI), skeletal muscle bioenergetics (muscle infrared spectroscopy), and patient-reported physical function (PROMIS instruments). Recruitment is ongoing; approximately 40% of the target sample has been enrolled, with seven participants having completed the intervention and follow-up.

Results: Preliminary work from our group suggests that SGLT2 inhibitors can improve skeletal muscle oxidative capacity, enhance fat utilization, and augment cardiac performance, supporting the mechanistic rationale for their use in early dysglycemia. Interim analyses from this trial are underway to assess reversion rates to euglycemia and changes in imaging, bioenergetic, and functional outcomes across treatment arms.

Conclusions: This randomized trial will determine whether empagliflozin, semaglutide, or combination metformin–pioglitazone, each paired with standardized nutritional counseling, more effectively promotes reversion from Pre-DM to euglycemia and improves cardiometabolic health compared with placebo in Hispanic adults. By integrating pharmacologic and lifestyle interventions with advanced phenotyping, this study seeks to define a scalable, mechanistically informed model for diabetes prevention and early cardiometabolic risk modification in a high-burden Hispanic population.

*Unless otherwise noted, all abstracts presented at ENDO must not be released to the press or the public until the date and time of presentation. For oral presentations, the abstracts are embargoed until the session begins. The Endocrine Society reserves the right to lift the embargo on specific abstracts that are selected for promotion prior to or during ENDO.*