Synergistic SGLT2 and GLP-1R targeting alleviates systemic inflammation-induced and M1 monocyte-driven endothelial dysfunction in coronary artery disease
Authors' conclusion
CAD features systemic inflammation that drives monocyte activation and endothelial dysfunction. Combined SGLT2i and GLP-1Ra synergistically suppress monocyte pro-inflammatory and pro-thrombotic activity and subsequently driven endothelial dysfunction.
Study context
- Population
- Healthy individuals, patients with CVD without coronary artery disease (CAD), and patients with stable CAD; plasma and circulating monocytes analysed
- Participants
- 20 / 20 / 55
- Comparison
- SGLT2 inhibitors (SGLT2i), GLP-1 RA and combined treatment on CAD plasma- and monocyte-induced endothelial dysfunction
- Healthyn = 20reference
- CVD without CADn = 20
- Stable CADn = 55
- Outcome
- Effects of SGLT2i and GLP-1 RA on CAD-induced monocyte activation and endothelial dysfunction
Main finding
As reported in the abstract
Combined treatment reduced CAD plasma-induced endothelial oxidative stress
≈80%
Combined treatment reduced CAD monocyte oxidative stress
≈82%
Further findings
CAD plasma inflammatory profile and endothelial effects
- CAD plasma showed increased IL-1β, IL-6, TNF-α, MCP-1, sICAM-1 and VCAM-1, with proteomic enrichment in complement, innate immune and extracellular matrix remodelling pathways
- CAD plasma induced endothelial oxidative stress, reduced nitric oxide, increased leukocyte and platelet adhesion and procoagulant activity, correlating with circulating TNF-α and sICAM-1
CAD monocyte phenotype
- CAD monocytes showed a metabolically activated phenotype (increased oxidative stress, mitochondrial activity, glucose and cholesterol uptake, calcium signalling, procoagulant activity, endothelial adhesion), correlating with TNF-α, sICAM-1 and plasma-induced endothelial dysfunction
- CAD monocytes showed increased NF-κB, NOX2 and NLRP3 signalling, reduced CREB/NRF2 pathways and elevated pro-inflammatory cytokines; their conditioned medium induced endothelial oxidative stress and blunted nitric oxide production
Original publication
Synergistic SGLT2 and GLP-1R targeting alleviates systemic inflammation-induced and M1 monocyte-driven endothelial dysfunction in coronary artery disease. Cardiovasc Diabetol. Published 4 July 2026. doi:10.
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