Metformin use is associated with reduced mortality risk in diabetic patients with Parkinson's disease

Introduction: Parkinson's disease (PD) and type-2 diabetes (T2D) arguably share pathophysiologic mechanisms, resulting in a more severe phenotype and progression and diabetes is currently considered a risk factor of PD. Besides, research suggests antidiabetic therapies as potential disease-modifying strategies. The main aim was to assess the impact of a metformin-inclusive antidiabetic treatment on patient all-cause mortality. Methods: A nested case-control prospective study including newly diagnosed PD patients reporting the onset of T2D within +/- 2 years from the onset of PD (n = 159) and matched (1:5; gender, year of PD onset and age at PD onset) non-diabetic cases (n = 795) followed until death or censoring. Patients on a metformin-inclusive treatment regimen were compared to those receiving other oral anti-diabetics (OADs). Results: Among patients with T2D, 123 were treated with a drug regimen containing metformin (alone [65.0%] or in combination with other drugs [35.0%]) and 36 were prescribed other OADs. During a median PD duration of 96 months [IQR, 60-144], 171 patients died. Diabetes was not associated with reduced survival: fully-adjusted HR = 1.19 [95%CI, 0.81-1.76] (P = 0.37). After stratifying for T2D treatment, a metformin-inclusive regimen was not associated with increased risk of death (HR = 1.06 [95%CI, 0.61 -1.84]; P = 0.83), while patients receiving other OADs had reduced survival (HR = 1.83 [95%CI, 1.01 -3.32]; P = 0.034). Conclusions: Metformin use was not associated with increased risk of death in diabetic patients with PD reporting concomitant onset of the two diseases. Metformin appears to be a promising diseasemodifying therapy given also the preclinical background, low cost and satisfactory safety and tolerability. Further studies are warranted to investigate its impact on disease progression. (c) 2024 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd. All rights reserved.