Systemic Effects of GLP-1 and Dual GIP/GLP-1 Receptor Agonism in Obesity, Cardiovascular Health, and Neurodegeneration

Review Article

Abstract

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and the novel dual GIP/GLP-1 receptor agonists have transcended their initial designation as merely anti-hyperglycemic agents to become pivotal tools in the management of systemic metabolic pathology. The transition from Liraglutide to Semaglutide, and subsequently to the dual agonist Tirzepatide, marks a paradigm shift in pharmacotherapy, moving from glucocentric control to substantial adiposity reduction and end-organ protection. Clinical data indicates that these agents facilitate weight loss magnitudes previously attainable only through bariatric intervention, primarily via central mechanisms involving the hypothalamus and hindbrain to regulate satiety and energy expenditure. Beyond anthropometrics, recent landmark outcomes, particularly from the SELECT trial, demonstrate that Semaglutide confers significant cardiovascular protection in non-diabetic individuals with obesity, reducing major adverse cardiovascular events through mechanisms distinct from weight loss alone, including anti-inflammatory pathways and endothelial stabilization. Moreover, emerging research suggests these peptides cross the blood-brain barrier to mitigate neuroinflammation and enhance neuronal insulin signaling, offering potential disease-modifying effects in Alzheimer’s and Parkinson’s disease. These findings point towards a unified therapeutic strategy addressing the intersection of metabolic, cardiovascular, and neurological health.