José Luis Lanciego
Senior Researcher of the Gene Therapy in Neurodegenerative Diseases Programme at the Centre for Applied Medical Research (CIMA), University of Navarra
A study by French neurologists has evaluated the efficacy of a drug commonly used in the treatment of type 2 diabetes mellitus to control blood glucose levels as a potential treatment for Parkinson's disease. It is a double-blind clinical trial with lixisenatide, a GLP-1 receptor agonist drug (trade name Lyxumia). It is a 're-use' trial, i.e. a drug already approved for the treatment of another indication (type 2 diabetes mellitus) is tested for a specific disease (Parkinson's in this case), so that this type of trial already has a high level of safety from the outset.
A total of 178 patients diagnosed with Parkinson's less than three years ago were recruited for this study and randomly assigned to either the control or placebo group. The doses of lixisenatide used were the usual doses for the treatment of diabetes, starting with an initial dose of 10 micrograms for 14 days and continuing with a maintenance dose of 20 micrograms for 12 months. The drug is self-administered by a pen injected subcutaneously into the thigh, abdomen or upper arm (the injection site is not reported in the article).
The aim is to find out whether the administration of lixisenatide slows the progression of Parkinson's disease by comparing the scores obtained on clinical scales between the treated group and the control group. The most relevant finding is that at 12 months of treatment, the score on the motor scales is 3 points lower in the treated patients compared to the patients in the placebo group. The clinical scale used is the MDS-UPDRS III, where the higher the score, the greater the severity.
Although the 3-point improvement is unremarkable, it is statistically significant. However, it is necessary to consider whether this improvement is of sufficient clinical benefit, as there are several side effects such as nausea, vomiting and gastro-oesophageal reflux (present in 46%, 13% and 8% of patients treated with the drug, respectively), gastrointestinal side effects commonly reported in identically treated diabetic patients. Note that side effects were considered unacceptable in approximately one-third of lixisenatide-treated patients, necessitating a reduction of their maintenance medication (20 micrograms) to the starting dose (10 micrograms).
Among the limitations of the study, it should be noted that all patients were treated with various types of antiparkinsonian medication during the clinical trial, so it is difficult to assess whether the modest benefit obtained with lixisenatide is due to that drug or to the antiparkinsonian medication itself. It is also necessary to take into account that the follow-up time is too short (12 months) to properly assess whether or not lixisenatide has a long-term effect. Furthermore, only the dosing regimen recommended for the treatment of diabetes mellitus was used, without considering other dosing regimens.
In conclusion, and as the authors themselves acknowledge, clinical trials with a larger number of patients and over a longer period of time will be necessary to properly determine the efficacy and safety of this potential re-use treatment for Parkinsonian patients.