Diabetic issues Drug Reveals Profit in Parkinson’s Disease

Diabetic issues Drug Reveals Profit in Parkinson’s Disease

— Stage II review of GLP-1 drug lixisenatide fulfills main endpoint

by Judy GeorgeDeputy Managing Editor, MedPage These days

The glucagon-like peptide-one (GLP-1) receptor agonist lixisenatide (Adlyxin) led to less progression of motor incapacity compared with placebo in early Parkinson’s illness, the period II LIXIPARK trial showed.

At 12 months, motor scores on the Motion Disorder Modern society-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) part III enhanced by .04 factors in the lixisenatide team and worsened by 3.04 details in the placebo group, a variation of 3.08 details (95% CI .86-5.30, P=.007), noted Olivier Rascol, MD, PhD, of the University of Toulouse in France, and co-authors.

Nausea transpired in forty six% and vomiting in 13% of lixisenatide-treated members, the researchers claimed in the New England Journal of Medication. Secondary endpoint benefits did not vary significantly between groups.

“In participants with early Parkinson’s disorder, lixisenatide therapy resulted in less progression of motor incapacity than placebo at 12 months in a stage II trial but was associated with gastrointestinal side effects,” Rascol and colleagues wrote. “Lengthier and greater trials are desired to figure out the outcomes and basic safety of lixisenatide in folks with Parkinson’s condition.”

The GLP-1 receptor is current in the mind, and agonist activity is assumed to be anti-inflammatory by lessening microglia activation. Observational research has shown that Parkinson’s incidence is reduced amid persons with diabetes treated with GLP-1 receptor agonists or dipeptidyl peptidase four (DPP4) inhibitors when compared with other diabetic issues medicine.

Quite a few GLP-one receptor agonists are staying examined as potential Parkinson’s solutions. A single-center trial of exenatide (Byetta, Bydureon) confirmed beneficial effects on motor function. A pegylated analogue of exenatide identified as NLY01 unsuccessful a period II demo but prompt positive aspects for people younger than 60.

“Creating a convincing demonstration of a condition-modifying, neuroprotective result in Parkinson’s illness is a difficult task,” noticed David Standaert, MD, PhD, at College of Alabama at Birmingham, in an accompanying editorial.

In LIXIPARK, the distinction in scores MDS-UPDRS scores after twelve months of lixisenatide procedure was statistically significant but modest, Standaert observed.

“The importance of this acquiring is not the magnitude of the change but what it portends. Indeed, the key issue of most individuals with Parkinson’s condition is not their current affliction — it is the fear of progression of the condition,” he wrote.

“If a 3-place improvement in score on the MDS-UPDRS is the most that can be realized with lixisenatide, then the value of procedure with the drug may well be constrained (primarily in view of the adverse results),” he pointed out. “On the other hand, if the benefit of lixisenatide is cumulative, adding a further three factors each 12 months in excess of a time period of 5 to 10 several years or far more, then this could be a truly transformative cure.”

Lixisenatide was authorized to address kind two diabetic issues in 2016. In 2023, drugmaker Sanofi claimed it would no for a longer time be marketed in the U.S. based mostly on a business enterprise determination, not for security or efficacy good reasons.

LIXI PARK enrolled 156 people whose Parkinson’s disorder had been diagnosed significantly less than three many years previously. All were on a stable dose of medications to take care of indications, and none had motor issues.

Contributors had been randomly assigned to day by day subcutaneous lixisenatide or placebo for twelve months (78 individuals in every team), followed by a 2-month washout interval. Demographics in each and every group were being similar, and the indicate length of disorder from the time of diagnosis was one.four a long time in both groups.

More than a third of participants (36%) in the lixisenatide team had unacceptable side results on the focus on dose of 20 μg for each day and switched to a lessened dose of ten μg for each working day.

The principal endpoint was the adjust from baseline in MDS-UPDRS aspect III scores — which range from to 132, with higher scores indicating higher motor incapacity — in the on-medicine point out at twelve months.

Baseline MDS-UPDRS aspect III scores ended up 14.eight in the lixisenatide team and fifteen.five in the placebo group. At thirty day period 14, indicate scores in the off-medication condition have been seventeen.7 with lixisenatide and twenty.6 with placebo.

Other secondary efficacy actions have been generally similar in the two groups at thirty day period 6 and month twelve. Signify alterations from baseline in the levodopa equivalent each day dosage were 35.eight mg per working day with lixisenatide and 31.3 mg for every day with placebo.

“The secondary endpoints provide no definite assistance for the key endpoint success, and longer washout durations may be needed to figure out regardless of whether lixisenatide therapy has a lengthy-lasting outcome,” the scientists mentioned. No imaging biomarkers were used in the examine, and whether or not any drug result on motor scores persists with for a longer period exposure or at other phases of Parkinson’s is unfamiliar.

Rascol and colleagues also famous that they “tested only one particular dose of lixisenatide, on the foundation of tips for the remedy of diabetes mellitus, and other doses may well have improved or worse effects in people with Parkinson’s sickness.”

  • Judy George covers neurology and neuroscience news for MedPage Now, crafting about mind getting older, Alzheimer’s, dementia, MS, unusual ailments, epilepsy, autism, headache, stroke, Parkinson’s, ALS, concussion, CTE, slumber, ache, and far more. Adhere to


This review was supported by grants from the French Ministry of Health and fitness and Treatment Parkinson’s, in partnership with the Van Andel Institute.

Rascol reported associations with AbbVie, Adamas, Biogen, Fundacao Bial, Lundbeck, Jazz, Sunovion, and Takeda. Co-authors also documented interactions with industry.

Standaert described interactions with AbbVie, Alnylam, Biohaven, BlueRock, Curium, F. Hoffmann La-Roche, Lilly United states, McGraw-Hill, Sanofi, and Theravance.

Principal Supply

New England Journal of Medication

Supply Reference: Meissner WG, et al “Demo of lixisenatide in early Parkinson’s disease” N Engl J Med 2024 DOI: ten.1056/NEJMoa2312323.

Secondary Source

New England Journal of Medication

Resource Reference: Standaert DG “GLP-one, Parkinson’s ailment, and neuroprotection” N Engl J Med 2024 DOI: 10.1056/NEJMe2401743.

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