Catherine Martinez, BA,

Anne-Marie Wills, MD, MPH

As the use of glucagonlike peptide1 receptor agonists (GLP1RAs) accelerates for weight loss and metabolic disease, these drugs are increasingly prescribed to patients with Parkinson’s disease (PD) who rely on oral levodopa for symptom control.

This overlap raises a timely concern: GLP1RAs delay gastric emptying and affect the absorption of many oral drugs, yet their impact on levodopa response in Parkinson’s disease patients has not been systematically studied. 

In a brief letter published in Movement Disorders Clinical Practice, Catherine Martinez, BA, and Anne-Marie Wills, MD, MPH, of the Mass General Brigham Neuroscience Institute describe two patients with Parkinson’s disease in which initiation of newer GLP1RAs was followed by marked changes in levodopa efficacy.

One patient with Parkinson’s disease developed a profound, food-dependent delay in levodopa “ON” time—the period when the medication is working and symptoms are controlled—after starting semaglutide, leading to unsupervised dose escalation and nighttime dyskinesias.

In the second case, the patient’s tremor no longer responded to levodopa after the patient started taking tirzepatide, prompting multiple medication changes with limited benefit.

In both patients, levodopa had previously provided stable symptom control for Parkinson’s disease. 

Although earlier trials of the GLP1RA exenatide in Parkinson’s disease did not show clear increases in dose failures, the authors hypothesize that newer agents may cause greater delays due to more pronounced gastrointestinal effects.

Given the rapid expansion of GLP1RA use, they underscore the need for formal study and heightened clinical awareness of potential interactions with oral Parkinson’s disease therapies. 

Published in Movement Disorders Clinical Practice on March 12, 2026 | Read the paper: “Levodopa Efficacy and GLP-1 Receptor Agonists” 

Summary reviewed by: Catherine Martinez, BA, lead author and Anne-Marie Wills, MD, MPH, senior author