Semaglutide Investigated for Improving Endothelial Progenitor Cells and Fat-Derived MSCs in Type 2 Diabetes

Type 2 Diabetes Mellitus (T2DM) significantly impairs cardiovascular health, largely due to the detrimental effects of high glucose on endothelial progenitor cells (EPCs). These CD34+ EPCs are crucial for maintaining the integrity of blood vessel linings, and their dysfunction contributes to adverse cardiovascular outcomes. Current T2DM treatments often fall short in directly addressing EPC health and mitochondrial function in adipose-derived mesenchymal stem cells (MSCs), which are also implicated in metabolic health and weight management. This study aims to explore whether Semaglutide, a GLP-1 receptor agonist, can bridge this gap by enhancing EPC number, function, and gene expression, alongside improving MSC mitochondrial metabolism.

This randomized, placebo-controlled clinical trial will enroll 40 subjects with T2DM on metformin. Participants are randomized to active Semaglutide or placebo. The study drug up-titration spans 9 weeks: 0.25 mg/week (weeks 0-4), 0.5 mg/week (weeks 5-8), then 1 mg/week (weeks 9-24). Key assessments include body composition (Tanita scale), arterial stiffness, and blood draws for EPC cell analysis and standard labs. Fat biopsies (2-3 grams) from the belly area at Visit 1 (week 0) and Visit 3 (week 24) will analyze fat-derived MSCs.