Reacción a "Reactions to phase 2 clinical trial testing an oral antidiabetic as a treatment for Parkinson's disease"

This is a randomised, double-blind, placebo-controlled phase II clinical trial to demonstrate the neuroprotective effect of an anti-diabetic drug in Parkinson's disease. The drug in question, lixisenatide, is a GLP1 receptor agonist, used as an anti-diabetic, which has demonstrated a neuroprotective effect in preclinical models of the disease. In addition, other molecules of the same family have already been studied with the same objective, with dubious results. The study is well designed and with a sufficient patient sample to support the results and conclusions. In addition, the follow-up time is reasonable (up to one year) and the compliance rate is very high, which adds to the robustness of the study. 

Although we have very effective symptomatic treatments for Parkinson's disease, there is currently no drug that has demonstrated a net reduction in progression. Finding a molecule that can slow the progression of the disease is a major goal of research in Parkinson's disease and other neurodegenerative diseases, and this preliminary evidence provides hope for a drug that can slow the disease. This not only has a direct clinical impact (which is in fact slight), but, if the results are confirmed, it would point the way to a promising therapeutic target for further research into an effective therapy. 

There are some important limitations: 

1. Patients were already receiving medication at the time of recruitment, and this may have some impact on the results. However, given that patients at that stage of the disease would need to be started on medication during follow-up, it is reasonable that already treated patients were included. 
2. The main outcome assessments of the trial have been done at the so-called on stage, i.e. when the symptomatic medication previously taken by the patient is taking effect. Again, this complicates interpretation, but it is also a measure that has allowed for greater uniformity of assessments. 
3. The trial shows a small but significant effect on the motor symptoms of the disease, but no change in the so-called non-motor symptoms (such as depression, anxiety, apathy, sleep disturbance...), which, a priori, should improve in the same way as motor symptoms, although in an early diagnosis population such as the trial it is possible that patients had so few non-motor symptoms that it was very difficult to detect a change (because of the so-called 'floor effect'). 
4. The trial bases all its results on a clinical scale which, although the most widely used in Parkinson's disease progression, has certain limitations. Among them, there is some inter-observer variability, it does not take much account of the patient's point of view and it is not based on objective quantifiable data. Today we have objective means that can support clinical assessments, either at the neuroimaging level, or at the level of biological markers or objective motor quantification that eliminate the subjectivity of the scales. 
5. Potentially drug-related adverse effects were more frequent in the treated group than in the placebo group. Beyond the possible implications for drug tolerability, the mere presence of these effects may have produced an unblinding bias (by presenting these adverse effects, patients are more likely to believe they are taking the drug and not the placebo, reducing the value of the double-blind and placebo comparison). 
6. Finally, the trial shows a possible neuroprotective effect on disease progression, which would be a major revolution in the treatment of Parkinson's disease. This possible conclusion still needs to be confirmed at least (i) in another international multicentre phase III trial with a larger number of patients and (ii) after excluding more strongly that the observed effects are not due to a symptomatic impact (improvement of symptoms and not of the underlying disease), especially considering that some studies suggest that this molecule can increase dopamine levels.