Metformin Linked to Better Motor Function in Parkinson's

Pauline Anderson

May 29, 2020

Researchers are taking a closer look at whether the diabetes medication metformin might convey benefit in patients with both Parkinson's disease (PD) and diabetes — and are finding some positive signals.

A small retrospective study showed that patients with PD and diabetes who took the antihyperglycemic agent performed significantly better on tests of motor and nonmotor function than their counterparts who did not.

These results "provide a soft footprint" of the potential protective effects of metformin in PD, said investigator Daniele Urso, MD, clinical research fellow, Neurodegeneration Imaging Group, King's College London, United Kingdom.

The findings were presented at the Congress of the European Academy of Neurology (EAN) 2020, which transitioned to a virtual/online meeting because of the COVID-19 pandemic.

Shared Mechanisms

Emerging evidence points to a link between PD and diabetes, and highlights the many shared pathological mechanisms, such as neuroinflammation and neurogenesis, Urso said.

Observational studies have shown that individuals with diabetes are at increased risk of developing PD; and when they do, they experience more severe motor and nonmotor symptoms such as cognitive impairment compared with nondiabetic patients with PD.

The observed link between diabetes and PD has generated the research hypothesis that antidiabetic drugs such as metformin might be neuroprotective and even disease modifying in PD.

The current retrospective cohort study included 19 de novo PD patients (85% men; mean age, 65 years) with diabetes mellitus from the Parkinson's Progression Markers Initiative (PPMI) cohort.

The landmark PPMI is a multisite observational clinical study evaluating patients using advanced imaging, biological sampling, and clinical and behavioral assessments to identify biomarkers for PD progression.

Data and samples acquired from study participants are available to the scientific community to conduct research.

Urso and his colleagues stratified patients into two groups matched by age, sex, and PD disease duration: those not taking metformin (n = 11) and those taking metformin for more than 2 years (n = 8)

All participants had been diagnosed with PD within the past year. Those not taking metformin had been diagnosed with diabetes for about 6.8 years compared with 11.1 years for those taking the medication.

The Metformin Cumulative Dose, which is the metformin daily dose times the number of days of treatment, was used to investigate the potential association of dose with clinical features.

Potentially Protective

Results showed that compared with the patients not taking metformin, those taking the drug had a significantly better Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) total score (P = .04) and Benton Judgement of Line Orientation score, which assesses visuospatial function (P = .04).

These patients also did significantly better on certain measures of cognitive impairment, including the Symbol Digit Modalities Test score (P = .03) and the Semantic Fluency total score (P = .003). A higher metformin cumulative dose was associated with the MDS-UPDRS rigidity score.

The results suggest "a potential protective effect of metformin in PD," Urso said.

However, "further studies in de novo and prodromal PD patients are needed to provide a rationale for repurposing this drug," he added.

Asked by an online meeting attendee whether the researchers looked at vitamin B12 levels, Urso said they did not.

The question is pertinent as recent studies have suggested that B12 deficiency is common in patients with both PD and neuropathy, and that B12 levels decline over the course of PD. This has led some experts to hypothesize that B12 deficiency may contribute to overall decline in some patients.

More Appealing?

Session chair Joaquim Ferreira, MD, PhD, associate professor of neurology and clinical pharmacology, University of Lisbon, Portugal and head of the Laboratory of Clinical Pharmacology and Therapeutics in Lisbon, noted that such positive findings might generate calls to doctors from patients with PD inquiring about taking metformin.

Since metformin is an old antidiabetic drug that has proven safe and is available at any pharmacy, positive studies such as this new one may make it seem "even more appealing" as a potential agent to prevent or treat PD, Ferreira later told Medscape Medical News.

"It should be stated very clearly that these results do not allow us to conclude that metformin, or any other antidiabetic drug, is efficacious and should be prescribed for the treatment of PD," he said.

The study did have some positive elements, Ferreira added. For example, it used the PPMI, which is "a well-known and good quality cohort of early stage PD patients," he noted.

The research is "for sure another interesting piece of information" that links diabetes with PD, and it should reinforce interest in further studies of the potential benefits of antidiabetic drugs in patients with PD, Ferreira said.

However, although the study showed better outcomes in terms of PD symptoms and cognition in participants taking metformin, "the study methodology limits our capacity to conclude that metformin is the cause of this apparent benefit," he said.

The PPMI is sponsored by The Michael J. Fox Foundation for Parkinson's Research.

Congress of the European Academy of Neurology (EAN) 2020. Oral Session. Presented May 25, 2020.

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