Recent evidence suggests that there exists a close link between type 2 diabetes mellitus and Parkinson’s disease. It has been shown that the risk of developing Parkinson’s disease is 35% higher in type 2 diabetes mellitus patients.¹ Furthermore, patients with both Parkinson’s disease and diabetes have a worse prognosis in terms of motor and cognitive function.^2,3 Since the two diseases potentially share one common mechanism, both resulting from protein aggregation caused by dysregulation of cellular clearing systems, Seong Ho Jeong, et al. (Department of Neurology, Yonsei University College of Medicine, South Korea) recently hypothesized that some treatments for diabetes may also have a positive effect on patients with Parkinson’s disease.⁴

A new lead – a hypoglycaemic agent with neuroprotective properties

Dipeptidyl peptidase-4 inhibitors (DPP4i) are widely used potent hypoglycaemic agents that improve glucose metabolism. Their neuroprotective properties, mostly exerted via pleiotropic effects, have lately gained researcher’s interest, and a case‑control study already showed that DPP4i treatment decreased the risk for Parkinson’s disease.⁵ Hence, Dr Jeong and his team decided to investigate the protective effects of DPP4i on the nigrostriatal dopamine system in diabetic and non‑diabetic patients with de novo Parkinson’s disease.⁴

Potential effect on nigrostriatal dopamine system

To test the hypothesis that DPP4i confers protective effects on the nigrostriatal dopamine system, the researchers performed a comparative analysis of striatal dopamine transporter (DAT) availability and clinical parameters of longitudinal disease progression. ⁴ To that end, a total of 697 drug-naïve patients with de novo Parkinson’s disease who had previously undergone DAT imaging were retrospectively divided into three groups: diabetic patients with (n=54) or without (n=85) DPP4i treatment and non-diabetic patients (n=558).

Parkinson’s patients benefit from diabetic treatment

The team around Dr Jeong could show that diabetic Parkinson’s patients with DPP4i treatment had a higher baseline DAT availability in the anterior, posterior and ventral putamina compared with the diabetic patients without DPP4i treatment. ⁴ In addition, DPP4i-treated patients showed a slower longitudinal increase in the levodopa-equivalent dose (LED) compared to the two other groups after adjusting for confounding factors like disease duration, vascular factors, total white matter hyperintensities (WMH) and baseline DAT availability in the posterior putamen. DPP4i treatment also led to a lower risk of developing levodopa-induced dyskinesia (LID) in comparison to diabetic patients without DPP4i treatment.

Potential use for non-diabetic Parkinson’s patients

These new findings suggest that DPP4i therapy might have beneficial effects on the baseline striatal dopamine depletion and on long-term motor outcomes in patients with both Parkinson’s disease and diabetes. ⁴ The results implicate an important function of DPP4i treatment: counteracting the detrimental effect of diabetes mellitus on nigrostriatal dopaminergic neurons. Additionally, the positive effects on nigral dopaminergic neurons and longitudinal motor performance point towards a potential use of DPP4i for non-diabetic patients with Parkinson’s disease. However, further studies with larger patient sample sizes will be needed to draw more solid conclusions in the future.

References

1. Xu Q et al. Diabetes Care. 2011;34:910–15
2. Cereda E et al. Neurology. 2012;78:1507–11
3. Petrou M et al. Acad Radiol. 2016;23:577–81
4. Jeong SH et al. Brain. 2021;144:1127–37
5. Svenningsson P et al. Mov Disord. 2016;31:1422–3