Objective: To evaluate the tolerability and clinical effects of newer antidiabetic drugs in individuals with Parkinson’s disease (PD) and Lewy body dementia (LBD).

Background: Parkinson’s disease (PD) is a progressive neurodegenerative disorder with an increasing prevalence. Patients with type 2 diabetes (T2D) are at higher risk of developing PD and tend to experience more severe motor dysfunction and faster disease progression. PD and T2D may share common pathophysiological mechanisms, such as protein aggregation, mitochondrial dysfunction, neuroinflammation, oxidative stress, and impaired insulin signaling. Dipeptidyl peptidase-4 (DPP4) inhibitors and sodium-glucose cotransporter-2 (SGLT2) inhibitors have demonstrated neuroprotective effects in preclinical studies, and show promise as potential therapeutic agents for PD. However, no prospective studies have evaluated these drugs in humans with PD or LBD.

Method: Twelve patients (mean age 69.6 ± 6.6 years) with PD or LBD participated in a 4-week randomized, placebo-controlled trial. Participants received either SGLT2 inhibitor therapy (dapagliflozin 10 mg daily), DPP4 inhibitor therapy (sitagliptin 100 mg daily), or placebo. Clinical assessments were performed at baseline and at the end of the study, including a neurological examination using the Movement Disorder Society Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) and a cognitive assessment using Mini-Mental State Examination (MMSE).

Results: All patients completed the study without serious adverse events. There were no significant differences in age, MDS-UPDRS or MMSE scores between groups at baseline. We remain blinded at this time. Although the study is small, differences were observed in the change in MDS-UPDRS total score at the end of the study (2.5 [1.5 to 6], vs. -3.5 [-7.1], vs. -7 [-18.5 to -4]; p = 0.0197). There were no statistically significant differences in MMSE scores between the groups.

Conclusion: SGLT2 inhibitors and DPP4 inhibitors are well tolerated in individuals with PD and LBD and may have beneficial effects on motor symptoms in PD. Further research is needed to evaluate the long-term effects of these antidiabetic medications in PD and their potential to modify disease progression.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/anti-diabetic-medications-to-fight-parkinsons-disease-and-lewy-body-dementia/