Big news with positive result announced for a randomized study of a GLP-1 agonist for Parkinson's just released @NEJM. A new era for Parkinson's or alternatively, more questions than answers raised by Meissner and colleagues. Key Points: - This multi-center French trial studied Lixisenatide which is a glucagon-like peptide-1 receptor agonist used for in diabetes. - The trial was a phase 2 double-blind randomized and placebo-controlled. - The authors wanted to know whether this drug would affect the progression of motor disability. - Who did they study? Parkinson's treated and with symptoms less than 3 years. - If you enrolled, you received daily subcutaneous lixisenatide or a placebo. - The primary outcome was a change in the motor PD scale called the MDS UPDRS when on dopamine medication after one year. - There were 78 people in each group. - The motor scores slightly improved in lixisenatide and worsened by 3 points in the placebo group. - There was a very short 2 month washout period where those getting the active drug stopped it and the benefit persisted. - Nausea was the most common side effect and occurred in about 1/2. My take: We have continued our multiple year love affair with various diabetes drugs and their potential links to Parkinson's disease, however the current study results are the most promising. Interpret with caution: there is a number called the 'clinically meaningful threshold' and those reading this study should appreciate that the results 'fell short' of this important metric. There will certainly be many arguments among experts as to whether this study met a minimum threshold for neuroprotection, and my personal opinion is that it did not. Here is an important message: In my view do not rush to prescribe this drug or try to creatively acquire it. We have been down this road many times including leukemia drugs, cough syrups and lithium. The data is not yet there to proceed to prescribing. More importantly, the weight loss associated with GLP-1’s is not desirable in the majority of cases of Parkinson’s disease and the nausea and vomiting will not be a welcome symptom. We must ask the important questions as to why the non-motor outcomes did not change, and why the other GLP-1 studies have been negative? Is there a blind spot here we are missing? Please appreciate this was trialed in only very early Parkinson's disease and thus there may be 'generalizablility' concerns. I do not want to diminish a great paper with a randomized design and encouraging data, however let's not rush to the drug store counter. Perhaps we should consider ad augusta per angusta – to glory through narrow spaces by continuing to follow the data with diabetes drugs and see where it leads and what it teaches us. nejm.org/doi/full/10.1056/NE… #Parkinsons #OZEMPIC #diabetes #GLP1