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Association Between GLP-1 Receptor Agonist Use and the Risk of Parkinson's Disease in Patients With Type 2 Diabetes
TAKE-HOME MESSAGE
- Although previous research has suggested that GLP-1 receptor agonists (GLP-1RAs) may have a disease-modifying effect on the development of Parkinson's disease (PD), the results of the population studies have not been consistent. The current study compared the risk of PD in older adults (age, ≥66 years) with type 2 diabetes (N = 89,074) based on whether they received GLP-1RAs (n = 30,091) or dipeptidyl peptidase 4 inhibitors (DPP4is; n = 58,983) using Medicare administrative data from 2016 to 2020. The crude incidence rate of PD was lower among GLP-1RA users than among DPP4i users. GLP-1RA users had a 23% lower risk of PD than DPP4i users.
- The study concluded that the new use of GLP-1RAs was significantly associated with a decreased risk of PD compared with DPP4is consistently across sex, race, and GLP-1RA types.
abstract
This abstract is available on the publisher's site.
Access this abstract nowBACKGROUND
Previous studies have suggested that glucagon-like peptide-1 receptor agonists (GLP-1RAs) may have a disease-modifying effect in the development of Parkinson's disease (PD), but population studies yielded inconsistent results.
OBJECTIVE
The aim was to compare the risk of PD associated with GLP-1RAs compared to dipeptidyl peptidase 4 inhibitors (DPP4i) among older adults with type 2 diabetes (T2D).
METHODS
Using U.S. Medicare administrative data from 2016 to 2020, we conducted a population-based cohort study comparing the new use of GLP-1RA with the new use of DPP4i among adults aged ≥66 years with T2D. The primary endpoint was a new diagnosis of PD. A stabilized inverse probability of treatment weighting (sIPTW)-adjusted Cox proportional hazards regression model was employed to estimate the hazard ratio (HR) and 95% confidence intervals (CI) for PD between GLP-1RA and DPP4i users.
RESULTS
This study included 89,074 Medicare beneficiaries who initiated either GLP-1RA (n = 30,091) or DPP4i (n = 58,983). The crude incidence rate of PD was lower among GLP-1RA users than DPP4i users (2.85 vs. 3.92 patients per 1000 person-years). An sIPTW-adjusted Cox model showed that GLP-1RA users were associated with a 23% lower risk of PD than DPP4i users (HR, 0.77; 95% CI, 0.63-0.95). Our findings were largely consistent across different subgroup analyses such as sex, race, and molecular structure of GLP-1RA.
CONCLUSION
Among Medicare beneficiaries with T2D, the new use of GLP-1RAs was significantly associated with a decreased risk of PD compared to the new use of DPP4i. © 2024 International Parkinson and Movement Disorder Society.
Additional Info
Disclosure statements are available on the authors' profiles:
Glucagon-Like Peptide-1 Receptor Agonists and Risk of Parkinson's Disease in Patients with Type 2 Diabetes: A Population-Based Cohort Study
Mov. Disord. 2024 Aug 27;[EPub Ahead of Print], H Tang, Y Lu, MS Okun, WT Donahoo, A Ramirez-Zamora, F Wang, Y Huang, M Armstrong, M Svensson, BA Virnig, ST DeKosky, J Bian, J GuoFrom MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
The current treatment options available for Parkinson’s disease (PD) remain exclusively for symptom management. However, ongoing research is directed toward preventing disease progression.
The pathogenesis of PD is thought to be driven by the formation of abnormal α-synuclein aggregates accompanied by immune activation, neuroinflammation, mitochondrial dysfunction, and changes in lysosomal and endosomal function.1 Multiple preclinical studies have shown that glucagon-like peptide-1 receptor (GLP-1R) agonists can interact with some of these processes and potentially inhibit dopaminergic loss, attenuate neuronal degeneration, reduce inflammation process, and thus prevent neurodegeneration in patients with PD.2 The advantage of GLP-1R agonists is that several are clinically approved for use in patients with diabetes, and thus an expedited approval for clinical use in patients with PD is possible if it is shown to be beneficial. Phase II clinical studies evaluating the use of GLP-1R agonists in treated patients with PD have been performed, although, to date, they have shown small or negative outcomes on PD rating scales but a good safety profile. Further studies are ongoing in patients with early-stage PD.3,4
The recently published article by Tang et al adds to the growing body of literature showing that GLP-1R agonists may have potential in patients with PD. The authors retrospectively reviewed a Medicare, US-based cohort (N = 89,074) of older adults with type 2 diabetes using glucose-lowering drugs and showed that GLP-1R agonist users had a lower incidence rate of PD diagnosis than those using DPP4 inhibitors (2.85 vs 3.92/1000 person-years), with a median follow-up period of 1.54 years for the former group and 1.75 years for the latter. Statistical analyses, using a stabilized inverse probability of treatment weighting to mitigate the effects of confounding, revealed that the reduction of PD risk in the GLP-1R agonist group was 23% (HR, 0.77). The authors address some of the limitations of previous epidemiological studies, which reported mixed results of the association between GLP-1R agonists and PD, by using an active comparator with a similar mechanism of action (DPP4 inhibitor), involving a larger population, and reducing the time bias by defining cohort entry as the first prescription of GLP-1R agonists or DPP4 inhibitors and identifying newer patients based on a 1-year washout period. It should be noted that no patients using lixisenatide, which is one of the GLP-1R agonists potentially associated with higher brain penetrance and less progression of PD symptoms compared with placebo, were included in this study.5 It might have been interesting to include the effects of other concomitant medications used by these individuals, including nonsteroidal anti-inflammatory drugs, statins, and β-blockers among others, which have also been suggested to be linked to PD risk, as cofounders.
We agree with the authors that future studies regarding the use of GLP-1R agonists should have a longer follow-up and more diverse populations, a recurrent conclusion in recent trials regarding the use of these drugs.5 However, the pathogenesis of PD remains heterogeneous and so are the multiple targets of the therapeutic pipeline,6 remembering the paradigm that “one size does not fit all.” Hopefully, this new evidence helps to build up a promising future for patients with PD and for improving their quality of life.
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