GLP-1-mediated delay in gastric emptying and impact on levodopa absorption in Parkinson's disease: Clinical...

Delayed gastric emptying is a well-recognized non-motor feature of Parkinson's disease (PD) and a critical determinant of levodopa pharmacokinetics. Glucagon-like peptide-1 (GLP-1) receptor agonists are increasingly prescribed for metabolic disorders and weight loss and are under investigation as potential disease-modifying therapies in PD. However, GLP-1 signaling exerts a potent inhibitory effect on gastric motility. This creates a mechanistic convergence whereby PD-related gastrointestinal dysfunction and GLP-1-mediated gastric slowing may synergistically impair transmission of levodopa and other dopaminergic drugs to the gut and thereby limit its efficacy. Here, we synthesize current evidence on the shared neuro-gastroenterological pathways linking PD and GLP-1 signaling, and we propose a conceptual "double-hit" model of delayed gastric emptying. We further examine the implications of this interaction for levodopa pharmacokinetics and motor fluctuations, highlighting a clinically relevant trade-off between the potential benefits of GLP-1 receptor agonists and their immediate negative impact on dopaminergic therapy.