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Ney Carter Borges: Mechanistic Insights and Clinical Cardiovascular Outcomes of GLP-1 Receptor Agonists
Ney Carter Borges/LinkedIn
Feb 21, 2026, 12:38

Ney Carter Borges: Mechanistic Insights and Clinical Cardiovascular Outcomes of GLP-1 Receptor Agonists

Ney Carter Borges, Member Cardiologist of Global Physician Association at Cleveland Clinic Florida, shared on LinkedIn about a recent article by Florian Kahles et al, published in The Journal of Clinical Investigation:

“GLP-1 and the cardiovascular system 

Mechanistic Insights and Clinical Cardiovascular Outcomes

Preclinical Cardiovascular Mechanisms

Atherosclerosis

  • Decreases Vascular inflammation
  • Decreases  Systemic inflammation
  • Decreases Monocyte and macrophage activation
  • Decreases Foam cell formation
  • Decreases Bone marrow hematopoiesis
  • Increases Fibrous cap thickness
  • Decreases Plaque size
  • Effects largely independent of LDL-C, blood pressure, and body weight

Experimental models (ApoE−/− and LDLr−/− mice) consistently demonstrate plaque stabilization and reduced atherogenesis through anti-inflammatory and vascular protective mechanisms

Heart Failure and Myocardial Protection

  • Decreases Ischemia–reperfusion injury
  • Decreases Cardiomyocyte apoptosis
  • Decreases Cardiac and systemic inflammation
  • Increases Myocardial glucose utilization
  • Increases Cardiac output during ischemic stress
  • Decreases Hypertrophy and fibrosis (HFpEF models)
  • Activation of PI3K/Akt, AMPK, PKC/S100A9 pathways

GLP-1R agonism improves post-MI survival and LV function across murine, porcine, and canine models

Major Cardiovascular Outcome Trials (CVOTs)

3-Point MACE Reduction (CV death, MI, Stroke)

Meta-analysis of 11 CVOTs

  • HR 0.86 (95% CI 0.80–0.93)
  • Relative Risk Reduction (RRR): 14%
  • NNT ≈ 65
  • p < 0.001

SELECT Trial (Obesity without T2D)

  • HR 0.80 (95% CI 0.72–0.90)
  • 20% RRR in MACE
  • 9% weight loss
  • 17,500 participants

SOUL Trial (Oral Semaglutide)

  • HR 0.86 (95% CI 0.77–0.96)
  • 14% RRR in MACE
  •  p = 0.006

Heart Failure Outcomes

  • Decreases Hospitalization for HF: HR 0.86 (95% CI 0.79–0.93)
  • FLOW trial (T2D + CKD):
  • Composite HF events: HR 0.73 (95% CI 0.62–0.87)
  • CV death: HR 0.71 (95% CI 0.56–0.89)

Clinical Interpretation

GLP-1 receptor agonists provide:

  1. Robust ASCVD risk reduction
  2. HFpEF symptom and functional improvement
  3. Modest BP and lipid improvements (insufficient alone to explain benefit)
  4. Anti-inflammatory and plaque-stabilizing effects
  5. Cardioprotection independent of glycemic control alone

The cardiovascular benefit emerges after 12–18 months, suggesting structural plaque modification rather than acute hemodynamic effects.

GLP-1 receptor agonists have evolved from glucose-lowering agents into cardiometabolic protective therapies with consistent reductions in MACE and meaningful benefits in heart failure—particularly HFpEF. Preclinical mechanistic data strongly align with clinical outcomes, establishing GLP-1–based therapy as a cornerstone of cardiovascular risk reduction in T2D, CKD, and obesity.”

Title: GLP-1 and the cardiovascular system

Authors: Florian Kahles, Andreas L. Birkenfeld, Nikolaus Marx

Read the Full Article on The Journal of Clinical Investigation.

Ney Carter Borges: Mechanistic Insights and Clinical Cardiovascular Outcomes of GLP-1 Receptor Agonists

Find more posts featuring Ney Carter Borges on Hemostasis Today.

Andreas L. Birkenfeld Cardiovascular System Florian Kahles GLP-1 Health Heart Failure Hematology Hemostasis Hemostasis News Hemostasis Today JCI Medicine Ney Carter Borges Nikolaus Marx The Journal of Clinical Investigation thrombosis
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