GLP-1 Receptor Agonists and Stimulant Medications

Introduction to GLP-1 Receptor Agonists

GLP-1 receptor agonists can affect stimulant absorption by delaying gastric emptying, which may impact the pharmacokinetics of concomitantly administered oral medications including stimulants, as noted by the American College of Cardiology and other medical guidelines 1, 2

GLP-1 receptor agonists affect drug absorption through several mechanisms, including delayed gastric emptying, which is mediated by GLP-1 receptors located on the myenteric plexus activating nitrergic and cyclic adenosine monophosphate pathways to inhibit vagal activity on the gut 2
GLP-1 receptor agonists also affect gastric motility, resulting in reduced phasic gastric contractions, delayed gastric emptying, reduced gastric acid secretion, and increased fasting and postprandial gastric volumes 2

Short-acting GLP-1 RAs (exenatide twice daily, lixisenatide) have more pronounced effects on gastric emptying than long-acting agents, which may impact stimulant absorption 2
Long-acting GLP-1 RAs (liraglutide, semaglutide, dulaglutide, albiglutide) experience tachyphylaxis (diminishing effect) on gastric emptying over time, which may reduce their impact on stimulant absorption 2

To optimize treatment when combining GLP-1 RAs with stimulant medications, consider separating the administration times of stimulants and GLP-1 RAs, and take stimulant medications at least 1-2 hours before GLP-1 RA administration when possible, as recommended by clinical guidelines 2
Monitor for changes in stimulant effectiveness when initiating or adjusting GLP-1 RA therapy, and be aware that stimulant effects may be delayed or reduced due to slower absorption 2
Dose adjustments of stimulants may be necessary when used concomitantly with GLP-1 RAs, considering the differential effects of short-acting versus long-acting GLP-1 RAs 2

The degree of interaction between GLP-1 RAs and stimulant medications may vary between patients and different GLP-1 RA formulations, and the clinical significance may vary based on the specific stimulant medication, GLP-1 RA used, and individual patient factors 2
Tachyphylaxis, or the diminishing effect of long-acting GLP-1 RAs on gastric emptying over time, may decrease the impact on stimulant absorption with continued use 2