{"product_id":"diabetes-drug-lixisenatide-shows-promise-in-slowing-early-parkinsons-disease-progression","title":"Diabetes Drug Lixisenatide Shows Promise in Slowing Early Parkinson's Disease Progression","description":"\u003cp\u003eIn a phase 2 clinical trial of 156 people with early Parkinson's disease, daily injections of lixisenatide (a diabetes drug) slowed the worsening of motor disability over 12 months compared with placebo. Motor scores improved slightly in the lixisenatide group but worsened in the placebo group, a statistically significant difference (P = 0.007). However, gastrointestinal side effects were common, with nausea in 46% and vomiting in 13% of participants taking lixisenatide. The authors conclude that longer and larger trials are needed before this treatment can be recommended.\u003c\/p\u003e\n\n\u003ch1\u003eDiabetes Drug Lixisenatide Shows Promise in Slowing Early Parkinson's Disease Progression\u003c\/h1\u003e\n\n\u003ch2\u003eTable of Contents\u003c\/h2\u003e\n\u003cul\u003e\n\u003cli\u003e\u003ca href=\"#ddn-key-points\"\u003eKey Points\u003c\/a\u003e\u003c\/li\u003e\n\n\u003cli\u003e\u003ca href=\"#background\"\u003eBackground: Why This Research Matters\u003c\/a\u003e\u003c\/li\u003e\n\u003cli\u003e\u003ca href=\"#study-methods\"\u003eHow the Study Was Conducted\u003c\/a\u003e\u003c\/li\u003e\n\u003cli\u003e\u003ca href=\"#key-findings\"\u003eKey Findings: What the Study Showed\u003c\/a\u003e\u003c\/li\u003e\n\u003cli\u003e\u003ca href=\"#side-effects\"\u003eSide Effects and Safety\u003c\/a\u003e\u003c\/li\u003e\n\u003cli\u003e\u003ca href=\"#clinical-implications\"\u003eWhat This Means for Patients\u003c\/a\u003e\u003c\/li\u003e\n\u003cli\u003e\u003ca href=\"#limitations\"\u003eLimitations: What the Study Could Not Prove\u003c\/a\u003e\u003c\/li\u003e\n\u003cli\u003e\u003ca href=\"#recommendations\"\u003eRecommendations and Next Steps\u003c\/a\u003e\u003c\/li\u003e\n\u003cli\u003e\u003ca href=\"#ddn-faq\"\u003eFrequently Asked Questions\u003c\/a\u003e\u003c\/li\u003e\n\u003cli\u003e\u003ca href=\"#source\"\u003eSource Information\u003c\/a\u003e\u003c\/li\u003e\n\u003c\/ul\u003e\n\n\u003c!-- ddn:keypoints:start --\u003e\n\u003ch2 id=\"ddn-key-points\"\u003eKey Points\u003c\/h2\u003e\n\u003cul\u003e\n\u003cli\u003eIn a 12-month trial of 156 people with early Parkinson's disease, daily lixisenatide injections slowed worsening of motor disability compared with placebo.\u003c\/li\u003e\n\u003cli\u003eMotor scores improved slightly with lixisenatide but worsened with placebo, a statistically significant difference of 3.08 points on the MDS-UPDRS part III.\u003c\/li\u003e\n\u003cli\u003eGastrointestinal side effects were common: nausea in 46% and vomiting in 13% of those taking lixisenatide, with 36% needing a dose reduction.\u003c\/li\u003e\n\u003cli\u003eThe benefit persisted after a 2-month washout, suggesting lixisenatide may affect underlying disease progression, though an effect on symptoms cannot be ruled out.\u003c\/li\u003e\n\u003cli\u003eThe authors conclude that longer and larger trials are needed before lixisenatide can be recommended for Parkinson's disease; it is currently approved only for type 2 diabetes.\u003c\/li\u003e\n\u003c\/ul\u003e\n\u003c!-- ddn:keypoints:end --\u003e\n\n\n\u003ch2 id=\"background\"\u003eBackground: Why This Research Matters\u003c\/h2\u003e\n\n\u003cp\u003eCurrent treatments for Parkinson's disease focus mainly on replacing dopamine to control symptoms. These treatments have not convincingly shown that they can slow the disease itself. This gap has driven researchers to look for new approaches.\u003c\/p\u003e\n\n\u003cp\u003eSeveral clues pointed scientists toward a class of diabetes drugs called GLP-1 receptor agonists. Epidemiologic studies (studies that track health patterns in large populations) found that people with type 2 diabetes had a higher risk of developing Parkinson's disease than people without diabetes. Researchers also found a link between alpha-synuclein aggregates (clumps of a protein that are the hallmark of Parkinson's disease) and insulin resistance in the brain.\u003c\/p\u003e\n\n\u003cp\u003eFurther supporting this connection, some studies showed that people with diabetes who took GLP-1 receptor agonists or dipeptidyl peptidase-4 (DPP-4) inhibitors had a lower prevalence of Parkinson's disease. This lower prevalence was compared with those who took other diabetes medications. These drugs work by increasing GLP-1 levels in the body.\u003c\/p\u003e\n\n\u003cp\u003eGLP-1 receptor agonists increase insulin secretion from pancreatic beta cells when glucose levels are high. They also inhibit glucagon secretion from pancreatic alpha cells. GLP-1 analogues can reach measurable concentrations in the brain. Some preclinical evidence suggests that activating GLP-1 receptors protects brain cells against cytokine-mediated apoptosis (programmed cell death triggered by inflammatory signals) and may stimulate the growth of new neurons.\u003c\/p\u003e\n\n\u003cp\u003eAt least six GLP-1 receptor agonists have been or are being tested as potential treatments for Parkinson's disease. A small single-center trial of the GLP-1 receptor agonist exenatide showed positive effects on motor function during the off-medication state (when participants were not taking Parkinson's medications). However, those positive effects were not seen when participants were in the on-medication state. A phase 2 trial of NLY01, a longer-acting form of exenatide, did not show benefits in people with early Parkinson's disease who were not receiving dopamine replacement therapy.\u003c\/p\u003e\n\n\u003cp\u003eLixisenatide is a 44-amino-acid peptide used to treat type 2 diabetes. Like exenatide, its formulation is based on a naturally occurring GLP analogue called exendin-4. Lixisenatide's affinity for the GLP-1 receptor is up to four times greater than that of human GLP-1. Neuroprotective actions of lixisenatide have been shown in animal models of Alzheimer's disease. In one study using a mouse model of Parkinson's disease, lixisenatide (but not exendin-4) reduced motor impairment and prevented the loss of dopamine neurons.\u003c\/p\u003e\n\n\u003cp\u003eBased on these findings, researchers designed the LIXIPARK trial to assess whether lixisenatide could modify the course of early Parkinson's disease in people who had already started standard treatment.\u003c\/p\u003e\n\n\u003ch2 id=\"study-methods\"\u003eHow the Study Was Conducted\u003c\/h2\u003e\n\n\u003cp\u003eThe LIXIPARK trial was an investigator-initiated, phase 2, multicenter, double-blind, parallel-group, randomized, placebo-controlled trial conducted in France. \"Double-blind\" means that neither the participants nor the investigators knew who received the active drug and who received the placebo. The trial included a 2-month washout period at the end (a period when participants stopped taking the trial drug).\u003c\/p\u003e\n\n\u003cp\u003eThe trial was coordinated by the Clinical Investigation Center of Toulouse University Hospital. Funding came from the French Ministry of Health and Prevention and Cure Parkinson's. The drug manufacturer Sanofi provided the drug and placebo and advised on expected drug characteristics and potential safety issues. Sanofi had no other role in conducting the trial, analyzing data, or writing the manuscript.\u003c\/p\u003e\n\n\u003cp\u003eStatistical analyses were performed independently by members of the European Clinical Trials Platform and Development (EUCLID)–F-CRIN clinical trials platform. The trial followed Good Clinical Practice guidelines, the principles of the Declaration of Helsinki, and French law. The protocol was approved by the ethics committee of Ile de France VII. All participants provided written informed consent.\u003c\/p\u003e\n\n\u003ch3\u003eWho Could Participate\u003c\/h3\u003e\n\n\u003cp\u003eParticipants were recruited from 21 of 25 centers in the French Clinical Research Network for Parkinson's Disease and Movement Disorders (NS-Park–F-CRIN). Eligible participants were 40 to 75 years of age and had received a Parkinson's disease diagnosis according to U.K. Brain Bank Criteria within the past 3 years.\u003c\/p\u003e\n\n\u003cp\u003eParticipants were already taking an optimized stable regimen of dopaminergic medication (dopamine agonist, levodopa, or monoamine oxidase B [MAO-B] inhibitor, or a combination). They had been on this regimen for at least 1 month before starting the trial agents and were expected to continue it for at least another 6 months.\u003c\/p\u003e\n\n\u003cp\u003eKey exclusion criteria included:\u003c\/p\u003e\n\u003cul\u003e\n\u003cli\u003eA score of at least 3 on the Hoehn and Yahr scale (range 1 to 5, with higher scores indicating worse disability), indicating at least mild-to-moderate bilateral motor involvement and some postural instability\u003c\/li\u003e\n\u003cli\u003eMotor fluctuations or dyskinesia (involuntary movements), or both\u003c\/li\u003e\n\u003cli\u003eAtypical or secondary parkinsonism\u003c\/li\u003e\n\u003cli\u003eA Montreal Cognitive Assessment (MoCA) score below 26 (range 0 to 30, with 26 or higher indicating normal cognitive function), suggesting at least mild cognitive impairment\u003c\/li\u003e\n\u003cli\u003eDiabetes mellitus (types 1 and 2)\u003c\/li\u003e\n\u003cli\u003ePrevious treatment with a GLP-1 receptor agonist\u003c\/li\u003e\n\u003cli\u003eHyperthyroidism or uncontrolled hypothyroidism\u003c\/li\u003e\n\u003cli\u003eSevere renal insufficiency (creatinine clearance below 30 ml per minute)\u003c\/li\u003e\n\u003cli\u003eActive liver disease\u003c\/li\u003e\n\u003cli\u003eSevere depression\u003c\/li\u003e\n\u003cli\u003eHistory of drug or alcohol abuse\u003c\/li\u003e\n\u003cli\u003eHistory of unexplained pancreatitis, chronic pancreatitis, or pancreatectomy\u003c\/li\u003e\n\u003cli\u003eBody-mass index below 18.5, malnutrition, or weight change greater than 5 kg within 3 months before screening\u003c\/li\u003e\n\u003c\/ul\u003e\n\n\u003ch3\u003eTrial Design and Treatment\u003c\/h3\u003e\n\n\u003cp\u003eParticipants were randomly assigned in a 1:1 ratio to receive either subcutaneous lixisenatide or placebo as an add-on to their current Parkinson's disease medications for 12 months. Randomization used a Web-based system with unstratified blocks of 4 and 6.\u003c\/p\u003e\n\n\u003cp\u003eAll participants were trained to use pens to inject themselves subcutaneously. The trial drug or placebo was administered 15 minutes before dinner each night. Lixisenatide or an equivalent volume of placebo started at 10 micrograms per day for 14 days. The dose then increased to 20 micrograms per day for the remainder of the 12-month period.\u003c\/p\u003e\n\n\u003cp\u003eParticipants who had adverse effects at the higher dose could continue at 10 micrograms per day until the end of the trial. Adherence to the assigned regimen was assessed through participant diaries and verified by pharmacies at the trial sites. Adherence was greater than 92.2% at all visits.\u003c\/p\u003e\n\n\u003cp\u003eParticipants continued their current Parkinson's disease medication regimen for at least the first 6 months of the trial. They were encouraged to keep the same regimen for the entire trial unless the investigator determined that a dose adjustment was needed.\u003c\/p\u003e\n\n\u003ch3\u003eAssessments and End Points\u003c\/h3\u003e\n\n\u003cp\u003eParticipants attended clinic visits at baseline, on day 15, and at months 1, 3, 6, 9, 12, and 14. Clinical assessments of Parkinson's disease were performed at baseline and at months 6 and 12.\u003c\/p\u003e\n\n\u003cp\u003eDuring assessment visits, participants in the on-medication state (receiving a stable dose of dopaminergic medication) were evaluated using:\u003c\/p\u003e\n\u003cul\u003e\n\u003cli\u003eThe Movement Disorder Society–sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) parts I through IV\u003c\/li\u003e\n\u003cli\u003eThe Parkinson's Disease Questionnaire summary index (PDQ-39; range 0 to 100, with higher scores indicating worse health status)\u003c\/li\u003e\n\u003cli\u003eThe Montreal Cognitive Assessment (MoCA)\u003c\/li\u003e\n\u003c\/ul\u003e\n\n\u003cp\u003eAt month 14, participants were assessed after a 2-month washout of the trial drug or placebo and an overnight washout of dopaminergic medication. This is called the practically defined off-medication state. Fasting blood glucose and insulin concentrations were measured at baseline and at months 6 and 12. Adverse events and vital signs were recorded at each visit.\u003c\/p\u003e\n\n\u003cp\u003eThe primary efficacy end point was the change from baseline to month 12 in scores on the MDS-UPDRS part III (the motor subscale; range 0 to 132). Higher scores on the MDS-UPDRS part III indicate greater severity of impairment. The scores were assessed in the on-medication state.\u003c\/p\u003e\n\n\u003cp\u003eSecondary efficacy end points included changes from baseline to months 6 and 12 in MDS-UPDRS parts I, II, and IV. Secondary efficacy end points also included change from baseline to month 12 in total MDS-UPDRS scores (sum of parts I, II, and III; range 0 to 236). Secondary efficacy end points also included change from baseline to month 6 in part III scores. The effect of lixisenatide on motor symptoms in the practically defined off-medication state was assessed as the between-group difference in motor scores at month 14.\u003c\/p\u003e\n\n\u003cp\u003eDoses of Parkinson's disease medication were prespecified to remain stable for the first 6 months. Dose changes were permitted during the second 6-month period and were considered an indicator of efficacy. A dose change was defined as a change from baseline to month 12 in the levodopa equivalent daily dose, calculated using published conversion ratios.\u003c\/p\u003e\n\n\u003ch3\u003eStatistical Analysis\u003c\/h3\u003e\n\n\u003cp\u003eBased on findings from a previous trial of exenatide in Parkinson's disease, researchers estimated a sample size of 158 participants (79 per group). This sample size would provide 80% power to detect a between-group difference of 4 points on the MDS-UPDRS part III. These calculations assumed a common standard deviation of 8, a dropout rate of 10%, and a two-sided type I error of 5%.\u003c\/p\u003e\n\n\u003cp\u003eEfficacy and safety end points were assessed in the modified intention-to-treat population, excluding participants with missing data. After confirming a normal distribution and homogeneous variances, researchers assessed efficacy using Student's t-test for quantitative variables. Given the small number of patients with missing data, analyses were conducted on available data without imputation.\u003c\/p\u003e\n\n\u003cp\u003eBecause there was no prespecified plan for adjusting the widths of confidence intervals for secondary end points, the intervals may not be used in place of hypothesis testing. No definite conclusions can be drawn from these secondary results.\u003c\/p\u003e\n\n\u003cp\u003eResearchers also performed linear regression analyses to assess whether baseline fasting blood glucose levels and insulin concentrations affected the primary end point. Because results from the phase 2 trial of NLY01 showed that age (under 60 years versus 60 years or older) may be a factor in response, they performed post hoc subgroup analyses. These post hoc subgroup analyses were of MDS-UPDRS motor scores with respect to these age groups.\u003c\/p\u003e\n\n\u003ch2 id=\"key-findings\"\u003eKey Findings: What the Study Showed\u003c\/h2\u003e\n\n\u003cp\u003eFrom February 2018 through March 2020, a total of 177 patients were screened at NS-PARK–F-CRIN sites. In March 2020, the steering committee decided to halt recruitment at 156 participants (instead of the planned 158). This decision was to avoid delays caused by the coronavirus disease 2019 pandemic and because of the low number of dropouts.\u003c\/p\u003e\n\n\u003cp\u003eA total of 157 participants were assessed for eligibility, and 156 (78 per group) were enrolled. One participant did not undergo randomization because he had shingles. A total of 7 participants discontinued lixisenatide or placebo across both groups, with no single reason as a common cause. All but 4 of the participants who discontinued were followed until month 12, and their outcomes were included in the primary analysis.\u003c\/p\u003e\n\n\u003cp\u003eOverall, 28 participants (36%) in the lixisenatide group had unacceptable side effects when receiving the target dose of 20 micrograms per day and switched to the reduced dose of 10 micrograms per day. One participant in the lixisenatide group and 3 in the placebo group had missing data for MDS-UPDRS part III scores at month 12. These results were not included in the primary analysis. Three participants (4%) in the placebo group had a dose reduction.\u003c\/p\u003e\n\n\u003ch3\u003eParticipant Characteristics at Baseline\u003c\/h3\u003e\n\n\u003cp\u003eThe demographic and clinical characteristics of participants at baseline were similar in the two groups and were typical of early disease. The mean duration of disease from the time of diagnosis was 1.4 years in both groups.\u003c\/p\u003e\n\n\u003cp\u003eThe mean MDS-UPDRS motor score at baseline was 14.8 (standard deviation 7.3) in the lixisenatide group and 15.5 (standard deviation 7.8) in the placebo group. The mean age was 59.5 years in the lixisenatide group and 59.9 years in the placebo group. The lixisenatide group was 56% male, and the placebo group was 62% male.\u003c\/p\u003e\n\n\u003cp\u003eOther baseline characteristics were similar between groups:\u003c\/p\u003e\n\u003cul\u003e\n\u003cli\u003eBody-mass index: 25.6 in the lixisenatide group versus 25.8 in the placebo group\u003c\/li\u003e\n\u003cli\u003eMDS-UPDRS part I (nonmotor aspects of daily living): 6.1 versus 6.4\u003c\/li\u003e\n\u003cli\u003eMDS-UPDRS part II (motor aspects of daily living): 5.0 versus 5.4\u003c\/li\u003e\n\u003cli\u003eMDS-UPDRS total (parts I, II, and III): 25.6 versus 27.0\u003c\/li\u003e\n\u003cli\u003eMDS-UPDRS part IV (motor complications): 0.3 versus 0.2\u003c\/li\u003e\n\u003cli\u003eMoCA score: 27.8 versus 28.1\u003c\/li\u003e\n\u003cli\u003ePDQ-39 score: 17.4 versus 16.8\u003c\/li\u003e\n\u003cli\u003eLevodopa equivalent daily dose: 317 mg versus 355 mg\u003c\/li\u003e\n\u003c\/ul\u003e\n\n\u003cp\u003eAll participants in the lixisenatide group and 97% in the placebo group were taking levodopa. MAO-B inhibitors were taken by 45% of the lixisenatide group and 41% of the placebo group. Dopamine agonists were taken by 69% of the lixisenatide group and 78% of the placebo group.\u003c\/p\u003e\n\n\u003ch3\u003ePrimary End Point Results\u003c\/h3\u003e\n\n\u003cp\u003eAt month 12, the mean score on the MDS-UPDRS part III in the on-medication state was 14.9 (95% confidence interval [CI], 13.3 to 16.6) in the lixisenatide group and 18.8 (95% CI, 16.6 to 21.0) in the placebo group.\u003c\/p\u003e\n\n\u003cp\u003eScores in the lixisenatide group improved from baseline by 0.04 points (95% CI, −1.62 to 1.54). Scores in the placebo group worsened by 3.04 points (95% CI, 1.46 to 4.62). The difference between groups was 3.08 points (95% CI, 0.86 to 5.30; P = 0.007). This means the result was statistically significant, with less than a 1% probability that it occurred by chance.\u003c\/p\u003e\n\n\u003cp\u003eAt month 14, after the 2-month washout period, the mean score on the MDS-UPDRS part III in the off-medication state was 17.7 (95% CI, 15.7 to 19.7) in the lixisenatide group. The mean score on the MDS-UPDRS part III in the off-medication state was 20.6 (95% CI, 18.5 to 22.8) in the placebo group.\u003c\/p\u003e\n\n\u003ch3\u003eSecondary End Point Results\u003c\/h3\u003e\n\n\u003cp\u003eResults for other secondary and exploratory efficacy measures were generally similar in the two groups at month 6 and month 12. Mean changes from baseline in the levodopa equivalent daily dosage were 35.8 mg per day (95% CI, 8.3 to 63.2) with lixisenatide and 31.3 mg per day (95% CI, 9.2 to 53.5) with placebo.\u003c\/p\u003e\n\n\u003cp\u003eThere were no apparent associations between baseline fasting blood glucose and insulin concentrations and scores on the MDS-UPDRS part III at month 12.\u003c\/p\u003e\n\n\u003cp\u003eA post hoc subgroup analysis, from which no conclusions can be drawn, showed that at month 12, lixisenatide had a numerically larger treatment effect in participants younger than 60 years of age. This treatment effect was larger than in those 60 years of age or older. The difference in MDS-UPDRS part III scores was 5.22 (95% CI, 1.95 to 8.48) in the younger group versus 1.00 (95% CI, −2.01 to 4.03) in the older group.\u003c\/p\u003e\n\n\u003ch2 id=\"side-effects\"\u003eSide Effects and Safety\u003c\/h2\u003e\n\n\u003cp\u003eAt least one adverse event was reported in a majority of participants: 86% of those who received lixisenatide and 71% of those who received placebo.\u003c\/p\u003e\n\n\u003cp\u003eGastrointestinal side effects were more common with lixisenatide than with placebo:\u003c\/p\u003e\n\u003cul\u003e\n\u003cli\u003eNausea: 46% with lixisenatide versus 12% with placebo\u003c\/li\u003e\n\u003cli\u003eVomiting: 13% with lixisenatide versus 3% with placebo\u003c\/li\u003e\n\u003cli\u003eGastroesophageal reflux: 8% with lixisenatide versus 1% with placebo\u003c\/li\u003e\n\u003c\/ul\u003e\n\n\u003cp\u003eThe incidence of serious adverse events was similar in the two groups, with five participants in each group experiencing a serious adverse event. Only one serious adverse event in each group was considered by the investigators to be treatment-related: pancreatitis in the lixisenatide group and syncope (fainting) in the placebo group.\u003c\/p\u003e\n\n\u003cp\u003eIn the lixisenatide group, six participants reported weight loss as an adverse event. No such adverse events were reported in the placebo group. However, no between-group difference was observed in the mean weight at any visit.\u003c\/p\u003e\n\n\u003cp\u003eOne case of hypoglycemia (low blood sugar) was reported in the placebo group. There were no reports of hypoglycemia with lixisenatide.\u003c\/p\u003e\n\n\u003cp\u003eA post hoc analysis showed that the presence of nausea apparently did not affect the magnitude of effect with respect to the primary end point in the lixisenatide group. However, no conclusions can be drawn from these results.\u003c\/p\u003e\n\n\u003ch2 id=\"clinical-implications\"\u003eWhat This Means for Patients\u003c\/h2\u003e\n\n\u003cp\u003eThis trial found that lixisenatide, a drug already approved for type 2 diabetes, slowed the progression of motor disability in people with early Parkinson's disease over 12 months. Participants taking lixisenatide had slightly improved motor scores, while those taking placebo had worsening motor scores.\u003c\/p\u003e\n\n\u003cp\u003eThe difference between groups was 3.08 points on the MDS-UPDRS part III. This is a modest but statistically significant difference. The MDS-UPDRS part III is a clinician-rated scale that measures motor impairment, with scores ranging from 0 to 132. A difference of about 3 points is below the threshold on this motor scale that other studies have considered clinically important to patients, though it came close to that threshold.\u003c\/p\u003e\n\n\u003cp\u003eImportantly, the benefit persisted after a 2-month washout period. At month 14, participants who had taken lixisenatide still had better motor scores in the off-medication state than those who had taken placebo. This suggests that lixisenatide may affect the underlying progression of Parkinson's disease, though the authors note that an effect on symptoms cannot be ruled out.\u003c\/p\u003e\n\n\u003cp\u003eHowever, gastrointestinal side effects were common. Nearly half of participants taking lixisenatide experienced nausea, and 13% experienced vomiting. More than one-third of participants in the lixisenatide group (36%) had side effects severe enough to require a dose reduction from 20 micrograms to 10 micrograms per day.\u003c\/p\u003e\n\n\u003cp\u003eThese side effects are important to consider. They may affect whether patients can tolerate the treatment and whether the benefits outweigh the discomfort.\u003c\/p\u003e\n\n\u003ch2 id=\"limitations\"\u003eLimitations: What the Study Could Not Prove\u003c\/h2\u003e\n\n\u003cp\u003eThis was a phase 2 trial, which means it was designed primarily to assess whether the treatment shows promise, not to provide definitive proof of effectiveness. Phase 2 trials are typically smaller and shorter than phase 3 trials, which are required before a treatment can be approved for widespread use.\u003c\/p\u003e\n\n\u003cp\u003eThe trial included 156 participants and lasted 12 months, with a 2-month washout period. The authors state that longer and larger trials are needed to determine the effects and safety of lixisenatide in people with Parkinson's disease.\u003c\/p\u003e\n\n\u003cp\u003eSeveral other limitations should be noted:\u003c\/p\u003e\n\n\u003cul\u003e\n\u003cli\u003eThe trial was conducted only in France, so results may not be generalizable to other populations.\u003c\/li\u003e\n\u003cli\u003eParticipants had early Parkinson's disease (diagnosed within 3 years) and were already receiving stable dopaminergic treatment. Results may not apply to people with more advanced disease or those not yet on treatment.\u003c\/li\u003e\n\u003cli\u003ePeople with diabetes were excluded from the trial, so results may not apply to them.\u003c\/li\u003e\n\u003cli\u003eThe trial was stopped early (at 156 participants instead of the planned 158) due to the COVID-19 pandemic, though the authors note this was a minor deviation.\u003c\/li\u003e\n\u003cli\u003eSecondary end points were not adjusted for multiple comparisons, so no definite conclusions can be drawn from those results.\u003c\/li\u003e\n\u003cli\u003eThe subgroup analysis suggesting a larger effect in people under 60 was a post hoc analysis, meaning it was not planned in advance. No conclusions can be drawn from this finding.\u003c\/li\u003e\n\u003cli\u003eThe trial did not include a diverse population in terms of race or ethnicity, as this information was not collected.\u003c\/li\u003e\n\u003c\/ul\u003e\n\n\u003ch2 id=\"recommendations\"\u003eRecommendations and Next Steps\u003c\/h2\u003e\n\n\u003cp\u003eBased on this trial, lixisenatide is not yet ready for routine use in Parkinson's disease. The authors conclude that longer and larger trials are needed to determine the effects and safety of lixisenatide in people with Parkinson's disease.\u003c\/p\u003e\n\n\u003cp\u003ePatients with Parkinson's disease should not ask their doctors to prescribe lixisenatide for Parkinson's disease based on this single phase 2 trial. The drug is currently approved only for type 2 diabetes.\u003c\/p\u003e\n\n\u003cp\u003eHowever, this trial provides encouraging evidence that GLP-1 receptor agonists may have a role in slowing Parkinson's disease progression. This is an active area of research, with at least six GLP-1 receptor agonists being tested for Parkinson's disease.\u003c\/p\u003e\n\n\u003cp\u003ePatients interested in participating in clinical trials of new Parkinson's disease treatments should talk to their neurologist about available options. ClinicalTrials.gov is a useful resource for finding ongoing trials.\u003c\/p\u003e\n\n\u003cp\u003eFor now, patients should continue their current Parkinson's disease treatment regimen as prescribed by their doctor. They should discuss any changes in symptoms or side effects with their healthcare provider.\u003c\/p\u003e\n\n\u003c!-- ddn:faq:start --\u003e\n\u003ch2 id=\"ddn-faq\"\u003eFrequently Asked Questions\u003c\/h2\u003e\n\u003ch3\u003eWhat did this trial find about lixisenatide for early Parkinson's disease?\u003c\/h3\u003e\n\u003cp\u003eIn a 12-month trial of 156 people with early Parkinson's disease, daily lixisenatide injections slowed worsening of motor disability compared with placebo. Motor scores improved slightly with lixisenatide but worsened with placebo, a statistically significant difference. However, the authors say longer and larger trials are needed before this treatment can be recommended.\u003c\/p\u003e\n\u003ch3\u003eWho was eligible to join this trial?\u003c\/h3\u003e\n\u003cp\u003eParticipants were 40 to 75 years old, diagnosed with Parkinson's disease within the past 3 years, and already taking a stable regimen of dopaminergic medication for at least 1 month. People with diabetes, significant cognitive impairment, motor fluctuations or dyskinesia, or certain other conditions were excluded. The trial was conducted in France.\u003c\/p\u003e\n\u003ch3\u003eWhat side effects did people taking lixisenatide experience?\u003c\/h3\u003e\n\u003cp\u003eGastrointestinal side effects were common. Nausea occurred in 46% of participants taking lixisenatide versus 12% taking placebo, and vomiting in 13% versus 3%. More than one-third of the lixisenatide group had side effects severe enough to reduce the dose from 20 to 10 micrograms daily. Serious adverse events were similar between groups.\u003c\/p\u003e\n\u003ch3\u003eWhat does the 3.08-point difference on the motor score mean?\u003c\/h3\u003e\n\u003cp\u003eThe MDS-UPDRS part III measures motor impairment from 0 to 132, with higher scores meaning worse function. Lixisenatide improved scores by 0.04 points while placebo worsened by 3.04 points, a between-group difference of 3.08 points. This is a modest but statistically significant difference, meaning it was unlikely due to chance.\u003c\/p\u003e\n\u003ch3\u003eDoes the benefit last after stopping the drug?\u003c\/h3\u003e\n\u003cp\u003eAfter a 2-month washout period, at month 14, participants who had taken lixisenatide still had better motor scores in the off-medication state than those who had taken placebo. This suggests that lixisenatide may affect the underlying progression of Parkinson's disease, though the authors note that an effect on symptoms cannot be ruled out.\u003c\/p\u003e\n\u003ch3\u003eCan I ask my doctor to prescribe lixisenatide for Parkinson's now?\u003c\/h3\u003e\n\u003cp\u003eNo. Based on this single phase 2 trial, lixisenatide is not yet ready for routine use in Parkinson's disease. The authors conclude that longer and larger trials are needed. The drug is currently approved only for type 2 diabetes. Patients should continue their current Parkinson's treatment as prescribed and discuss any changes with their doctor.\u003c\/p\u003e\n\u003ch3\u003eWhat are the limitations of this trial?\u003c\/h3\u003e\n\u003cp\u003eThis was a phase 2 trial of 156 people in France, so results may not apply to other populations or to those with more advanced disease or diabetes. It was stopped early due to COVID-19. Secondary and subgroup results were not adjusted for multiple comparisons, so no definite conclusions can be drawn from them. Longer and larger trials are needed.\u003c\/p\u003e\n\u003ch3\u003eI have early Parkinson's disease — should I get a second opinion before asking my neurologist about lixisenatide?\u003c\/h3\u003e\n\u003cp\u003eLixisenatide is approved only for type 2 diabetes and is not ready for routine use in Parkinson's disease. In a 12-month trial of 156 people with early Parkinson's disease, motor scores improved slightly with lixisenatide while placebo scores worsened, a modest but statistically significant difference, yet nausea occurred in 46% and vomiting in 13%, and 36% needed a dose reduction. Longer and larger trials are needed. A second opinion can help clarify whether your current regimen is appropriate and whether trial participation suits you. Diagnostic Detectives Network provides independent expert second opinions.\u003c\/p\u003e\n\u003c!-- ddn:faq:end --\u003e\n\n\u003ch2 id=\"source\"\u003eSource Information\u003c\/h2\u003e\n\n\u003cp\u003e\u003cstrong\u003eOriginal article title:\u003c\/strong\u003e Trial of Lixisenatide in Early Parkinsons Disease NEJM 2024\u003c\/p\u003e\n\n\u003cp\u003e\u003cstrong\u003eAuthors:\u003c\/strong\u003e W.G. Meissner, P. Remy, C. Giordana, D. Maltête, P. Derkinderen, J.-L. Houéto, M. Anheim, I. Benatru, T. Boraud, C. Brefel-Courbon, N. Carrière, H. Catala, M. Charif, O. Colin, J.-C. Corvol, P. Damier, E. Dellapina, D. Devos, S. Drapier, M. Fabbri, V. Ferrier, A. Foubert-Samier, S. Frismand-Kryloff, C. Geny, A. Georget, C. Germain, S. Grimaldi, C. Hardy, L. Hopes, P. Krystkowiak, B. Laurens, R. Lefaucheur, L.-L. Mariani, A. Marques, C. Marse, F. Ory-Magne, V. Rigalleau, H. Salhi, A. Saubion, S.R.W. Stott, C. Thalamas, C. Thiriez, M. Tir, R.K. Wyse, A. Benard, and O. Rascol, for the LIXIPARK Study Group\u003c\/p\u003e\n\n\u003cp\u003e\u003cstrong\u003ePublication:\u003c\/strong\u003e New England Journal of Medicine, 2024;390:1176-1185\u003c\/p\u003e\n\n\u003cp\u003e\u003cstrong\u003eDOI:\u003c\/strong\u003e 10.1056\/NEJMoa2312323\u003c\/p\u003e\n\n\u003cp\u003e\u003cstrong\u003eFunding:\u003c\/strong\u003e French Ministry of Health and Prevention and Cure Parkinson's. Sanofi provided the drug and placebo.\u003c\/p\u003e\n\n\u003cp\u003e\u003cstrong\u003eClinicalTrials.gov number:\u003c\/strong\u003e NCT03439943\u003c\/p\u003e\n\n\u003cp\u003e\u003cem\u003eThis patient-friendly article is based on peer-reviewed research.\u003c\/em\u003e\u003c\/p\u003e","brand":"DiagnosticDetectives.Com","offers":[{"title":"Default Title","offer_id":47919024570524,"sku":null,"price":0.0,"currency_code":"USD","in_stock":true}],"url":"https:\/\/diagnosticdetectives.com\/products\/diabetes-drug-lixisenatide-shows-promise-in-slowing-early-parkinsons-disease-progression","provider":"DiagnosticDetectives.Com","version":"1.0","type":"link"}