Trial results for semaglutide in patients with Type 2 Diabetes Mellitus were posted on ClinicalTrials.gov on 2025-09-09. The Phase 4 study investigated the impact of semaglutide on CD34+ endothelial progenitor cells (EPC) and fat-derived mesenchymal stem cells (MSC), showing increased gene expression of CD34+ EPCs in the active treatment group compared to placebo.
Background
Semaglutide is an FDA-approved medication for Type 2 Diabetes Mellitus. This study aimed to ascertain whether semaglutide could improve the number, function, and gene expression of subjects' CD34+ endothelial progenitor cells. EPCs are crucial for protecting the inner lining of blood vessels, and improving their survivability could enhance cardiovascular outcomes, as the high glucose environment of diabetes is toxic to these cells. The research also explored improving mitochondrial metabolism of Mesenchymal Stem Cells from subcutaneous fatty tissue, potentially leading to weight loss and overall vascular health improvement by reducing inflammation.
Trial design
The study (NCT04126603) was a Phase 4, completed trial with an enrollment of 10 participants diagnosed with Type 2 Diabetes Mellitus. Interventions included semaglutide and placebos.
Key results
The trial measured several outcomes related to endothelial progenitor cells and gene expression:
- CD34+ Endothelial Progenitor Cell Number (EPC) Per Mononuclear Cells (MNC) Ratio:
- For Group A Placebo, the mean ratio was 0.10 (Standard Deviation: 0.06).
- For Group B Active, the mean ratio was 0.23 (Standard Deviation: 0.16).
- In another measurement, Group A Placebo had a mean ratio of 0.12 (Standard Deviation: 0.03).
- Group B Active showed a mean ratio of 0.13 (Standard Deviation: 0.09).
- CD34+ Endothelial Progenitor Cell Migration (EPC) Against Serum SDF1a Gradient:
- For Group A Placebo, the mean migration was 708.5 micrometers (um) (Standard Deviation: 357.09).
- For Group B Active, the mean migration was 377.75 micrometers (um) (Standard Deviation: 440.17).
- In another measurement, Group A Placebo had a mean migration of 530.75 micrometers (um) (Standard Deviation: 405.53).
- Group B Active showed a mean migration of 3232.33 micrometers (um) (Standard Deviation: 2553.21).
- Gene Expression of CD34+ Endothelial Progenitor Cell Number:
- For Group A Placebo, the mean fold change was -0.64 (Standard Deviation: 0.72).
- For Group B Active, the mean fold change was 0.5 (Standard Deviation: 1.52).
- In another measurement, Group A Placebo had a mean fold change of 0.78 (Standard Deviation: 0.05).
- Group B Active showed a mean fold change of 1.49 (Standard Deviation: 0.43).
What this means
The results suggest that semaglutide may influence endothelial progenitor cell dynamics and gene expression in patients with Type 2 Diabetes Mellitus. Specifically, the observed increase in CD34+ EPC gene expression in the active group could indicate a potential benefit for vascular health, as EPCs play a role in protecting blood vessel linings. However, the small enrollment of 10 participants means these findings are preliminary and require further investigation in larger studies to confirm clinical significance and consistency across all measured parameters.
Source
The information regarding these trial results was obtained from ClinicalTrials.gov, a public database of clinical studies. The results for study NCT04126603, titled "Impact of Semaglutide on CD34+ EPC and Fat Derived MSC," were posted on 2025-09-09 on clinicaltrials.gov.