Sodium-glucose cotransporter 2 inhibitors and the risk of Parkinson disease in real-world patients with type 2 diabetes

Importance: Diabetes increases the risk of Parkinson disease (PD). Sodium-glucose cotransporter 2 (SGLT2) inhibitors, a new glucose-lowering therapeutic class, have shown neuroprotective effects in mechanistic studies. However, the association between SGLT2 inhibitors and PD risk in real-world populations with type 2 diabetes (T2D) remains unclear.

Objective: The aim was to assess the association between SGLT2 inhibitors and the risk of PD in older populations with T2D.

Design, setting and participants: This retrospective cohort analysis used Medicare claims data from 2016 to 2020 to identify fee-for-service beneficiaries ≥65 years diagnosed with T2D and without pre-existing PD.

Exposures: The initiation of an SGLT2 inhibitor was compared with that of a dipeptidyl peptidase-4 (DPP4) inhibitor.

Main outcomes and measures: The outcome was the first incident PD ever since the date initiating either an SGLT2 inhibitor or a DPP4 inhibitor. We employed a 1:1 propensity score matching to balance the baseline covariates between treatment groups, including sociodemographics, comorbidities and co-medications. We applied Cox regression models to assess the effect of SGLT2 inhibitors versus DPP4 inhibitors on incident PD.

Results: Of 89 330 eligible Medicare beneficiaries (mean age: 75 ± 7 years, 52% women), 0.6% (n = 537) had incident PD over the follow-up. After 1:1 propensity matching, the PD incidence was 2.5 and 3.5 events per 1000 person-years in the SGLT2 inhibitor group and DPP4 inhibitor group, respectively. The SGLT2 inhibitor group was associated with a significantly lower risk of incident PD than the DPP4 inhibitor group (hazard ratio: 0.70 [95% confidence interval: 0.55-0.89]). There is a potential trend that the risk reduction in incident PD was profound in non-Hispanic Black individuals and insulin users.

Conclusion and relevance: Compared to DPP4 inhibitors, SGLT2 inhibitors were associated with a significantly lower risk of incident PD in older populations with T2D.