A current research revealed within the New England Journal of Medication performed a trial of lixisenatide to evaluate its results in early Parkinson’s illness.
Examine: Trial of Lixisenatide in Early Parkinson’s Illness. Picture Credit score: create jobs 51/Shutterstock.com
Background
Present remedies for Parkinson’s illness are based on dopaminergic substitute remedy and haven’t convincingly demonstrated results on illness development. Additional, epidemiological research have noticed elevated Parkinson’s illness threat in people with kind 2 diabetes.
Furthermore, some research have proven a decrease prevalence of Parkinson’s illness amongst diabetes sufferers handled with dipeptidyl peptidase-4 inhibitors or glucagon-like peptide (GLP)-1 receptor agonists in comparison with recipients of different medicines.
Lixisenatide is a GLP-1 receptor agonist used to deal with kind 2 diabetes. Its neuroprotective actions have been demonstrated in animal fashions of Parkinson’s illness and Alzheimer’s illness.
In regards to the research
Within the current research, researchers evaluated the disease-modifying impact of lixisenatide in people with early Parkinson’s illness. This part 2, double-blind, randomized, multicenter, placebo-controlled trial was carried out in France.
Folks aged 40–75 recognized with Parkinson’s illness inside the previous three years have been recruited. Eligible topics have been handled with a steady, optimized dopaminergic remedy routine for a minimum of a month earlier than beginning trial brokers.
Members have been randomized to obtain lixisenatide or placebo along with their commonplace remedy for Parkinson’s illness.
The trial agent was initially administered at 10 μg/day for 14 days and 20 μg/day for the rest of 12 months. Topics continued their current remedy for Parkinson’s illness for the primary six months a minimum of.
Scientific assessments have been carried out at baseline, six-month, and 12-month visits. Topics have been evaluated in an on-medication state primarily based on scores on the Parkinson’s Illness Questionnaire abstract index, Motion Dysfunction Society (MDS)-sponsored revision of the Unified Parkinson’s Illness Score Scale (UPDRS) elements I–IV, and Montreal Cognitive Evaluation.
Moreover, topics have been assessed in an off-medication state after a two-month washout interval at 14 months.
Fasting blood glucose and insulin ranges have been measured. Very important indicators and antagonistic occasions have been recorded at visits. The first efficacy endpoint was the MDS-UPDRS half III scores change from baseline to 12 months.
Secondary efficacy endpoints have been the change in scores on MDS-UPDRS half III at six months, change in scores on MDS-UPDRS elements I, II, and IV at six and 12 months, and alter in whole MDS-UPDRS rating at 12 months. Efficacy was assessed utilizing Pupil’s t-test.
Linear regression analyses investigated the potential results of baseline ranges of fasting blood glucose and insulin on the first endpoint.
Findings
The research enrolled 156 topics; seventy-eight have been assigned to obtain lixisenatide, and the rest have been assigned to the placebo group. Within the lixisenatide arm, 28 topics have been switched again to the ten μg/day dose as a result of uncomfortable side effects on the 20 μg/day dose.
Additional, dose discount was required for 3 placebo recipients. Adherence to the trial agent was over 92% in any respect visits.
Members’ baseline scientific and demographic traits have been related between teams. In each teams, the typical time from prognosis was 1.4 years.
The typical baseline MDS-UPDRS motor rating was 14.8 in lixisenatide topics and 15.5 in placebo recipients. At 12 months, these scores have been 14.9 and 18.8 within the lixisenatide and placebo teams, respectively.
Lixisenatide recipients improved their rating by 0.04 factors from baseline, whereas placebo topics had worsened it by 3.04 factors. At 14 months, these scores have been 17.7 and 20.7 within the lixisenatide and placebo teams, respectively.
Outcomes for secondary/exploratory measures have been related between teams at six and 12 months. No associations have been noticed between fasting blood glucose and insulin ranges at baseline and MDS-UPDRS half III rating at 12 months.
Most individuals had a minimum of one antagonistic occasion. Gastrointestinal uncomfortable side effects have been extra prevalent with lixisenatide.
The 2 teams had an analogous incidence of great antagonistic occasions. One severe antagonistic occasion, syncope in placebo recipients and pancreatitis within the lixisenatide group was deemed treatment-related.
Conclusions
In sum, this part 2 trial confirmed that lixisenatide, administered in an on-medication state, had a three-point enchancment on a motor incapacity scale over 12 months in comparison with baseline.
This distinction was pushed by a rise in scores in placebo recipients. Additional, a three-point between-group distinction within the motor rating was noticed after the two-month washout interval, favoring energetic remedy.
Notably, the trial concerned topics with early illness; as such, it must be investigated whether or not drug results persist at different levels of the illness.
Furthermore, secondary endpoints didn’t definitively assist main endpoint outcomes; due to this fact, longer washout durations could also be crucial to check if the drug has long-lasting results.
Journal reference:
Meissner WG, Remy P, Giordana C, et al. (2024) Trial of Lixisenatide in Early Parkinson’s Illness. N Engl J Med,. doi: 10.1056/NEJMoa2312323.
