Newer diabetes medications may prevent Parkinson’s, study suggests

Meta-analysis favors more trials into select type 2 diabetes treatments

Steve Bryson, PhD avatar

by Steve Bryson, PhD |

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An illustration of oral medications.

Newer glucose-lowering drugs used to treat type 2 diabetes, compared with a placebo, appear to lower a person’s risk of Parkinson’s disease, according to a meta-analysis of controlled clinical trials.

Findings suggest a potential association between recent classes of anti-diabetic medications and the risk of developing Parkinson’s, and they support clinical studies evaluating glucose-lowering drugs as a Parkinson’s treatment, its scientists noted.

“Further studies using real-world data are required to confirm or refute this notion,” they wrote in the study, “Meta-Analysis of Association between Newer Glucose-Lowering Drugs and Risk of Parkinson’s Disease,” published in the journal Movement Disorders.

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Parkinson’s risk seen as elevated with diabetes, or poor glucose control

An elevated risk of Parkinson’s disease has been found among people with type 2 diabetes — a condition marked by excess glucose sugar levels in the blood because the body cannot make enough insulin. Insulin, a protein hormone, helps to control glucose levels, suggesting a potential relationship between glucose control and neurodegeneration.

Newer classes of glucose-lowering drugs are increasingly used to treat type 2 diabetes due to their ability to reduce the risk of cardiovascular and kidney disease. Such medications include glucagon-like peptide-1 receptor (GLP-1R) agonists, dipeptidyl peptidase-4 (DPP4) inhibitors, and sodium-glucose co-transporter-2 (SGLT2) inhibitors.

A recent study showed that Parkinson’s risk was 36-60% lower in diabetic patients receiving GLP-1R agonists or DPP4 inhibitors compared with other therapies. Building on such findings, several GLP-1R agonists approved to treat type 2 diabetes were evaluated for their ability to slow Parkinson’s progression.

For example, the medication lixisenatide showed a potential to slow progression of Parkinson’s motor symptoms in a Phase 2 trial. Liraglutide, approved to treat type 2 diabetes and obesity, improved patients’ mobility and activities of daily living.

However, the long-acting GLP-1R agonist NLY01 failed to slow motor symptoms in adults with early and untreated Parkinson’s disease in another Phase 2 study.

Scientists at the University of Florida further investigated connections between glucose-lowering drugs and Parkinson’s risk by combining the results of controlled trials, called a meta-analysis. These studies included people with and without type 2 diabetes, evaluating Parkinson’s risk was not their intent.

A database search yielded 24 clinical trials involving a total of 185,305 adults, with a mean age of 65.1, who were randomly assigned either a glucose-lowering drug or a placebo. Among them, 20 studies enrolled type 2 diabetes patients only, and four involved participants with or without diabetes. Five of these trials evaluated DPP4 inhibitors, eight investigated GLP-1 agonists, and 11 looked into SGLT2 inhibitors.

33 Parkinson’s cases identified over a median of 2.2 years in the trials

Across these studies, 33 cases of Parkinson’s were identified during follow-up that ranged from 0.8 to 5.4 years (median of 2.2 years).

Across all trials, the use of glucose-lowering drugs strongly associated with a 50% reduction in the risk of Parkinson’s compared with a placebo, the meta-analysis noted.

Examining each anti-diabetic medication independently, SGLT2 inhibitors were linked to a lower Parkinson’s risk against placebo, but the association was weak. There was no evidence that GLP-1 agonists and DPP4 inhibitors reduced the disease’s risk.

A subgroup analysis led to similar findings between trials that included type 2 diabetes patients only, as well as those enrolling adults with and without diabetes.

Researchers noted these findings “should be interpreted with caution,” due to the low number of people eventually diagnosed with Parkinson’s and the trials’ short follow-up period. Because diagnosing Parkinson’s can take three to 10 years, these cases may reflect established disease rather than the start of symptoms, they wrote.

Newer diabetes treatments help to ease oxidative damage and inflammation

Type 2 diabetes and Parkinson’s “share similar pathophysiological pathways, such as impaired insulin signaling, mitochondrial dysfunction, oxidative damage, and inflammation,” the researchers wrote. “Newer GLDs [glucose-lowering drugs] have generated significant interest for their neuroprotective effects by improving insulin resistance and reducing oxidative damage and inflammation, which make them promising therapeutic options” for managing Parkinson’s.

Oxidative damage, also called oxidative stress, is a type of cell damage caused by highly reactive oxygen-containing molecules and the body’s inability to neutralized them.

Statistical heterogeneity was not seen in the meta-analysis, meaning the studies included were similarly conducted with the same experimental protocols. There also was no evidence of publication bias, when the outcome of the clinical trials influenced the decision to publish.

“Our meta-analysis of outcome trials suggests that there may be a potential association between newer GLDs and a reduced risk of developing [Parkinson’s disease],” the scientists concluded. “Our findings also highlight the possibility of repurposing newer GLDs for the treatment of [Parkinson’s disease].”