Observational studyJournal of Parkinson's disease2025
SGLT2 inhibitors vs. metformin for Parkinson's disease risk reduction in type 2 diabetes.
Observational study in Journal of Parkinson's disease, 2025. The graph read 2 numbers from its abstract, feeding 2 cells of the map: it . Cited by 1 paper.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
SGLT2i users had significantly lower all-cause mortality (aHR = 0.85; 95% CI, 0.83-0.89; p < 0.0001).ConclusionsThis first large-scale comparison suggests SGLT2is provide superior neuroprotection against PD compared to metformin in T2DM patients, warranting further investigation.
Read, but not usablea number the graph found but could not read as for or against
Cox proportional hazards models estimated adjusted hazard ratios (aHRs), validated by positive and negative controls.ResultsSGLT2i use was associated with a 28% lower PD risk than metformin (aHR = 0.72; 95% CI, 0.62-0.84; p < 0.0001).
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Where it lands on the map
Rows are treatments, columns are outcomes. The coloured squares are the cells this paper feeds, coloured by the vote it casts there. Click one to jump to what this paper adds to it.
What it adds to each cell
For every cell the paper feeds: the belief in the claim with and without this paper, and this paper's estimate drawn against every other readable study in the cell. The ringed dot is this paper.
SGLT2 inhibitors×all-cause mortality
No readable resultOpen on the map →What to test next →13 readable studies in this cell: 5 favour the treatment, 6 find no difference, 2 favour the comparator.
This paper's own estimate is on a different scale from the rest of the cell, so it is not drawn here.
SGLT2 inhibitors×pharmacokinetics & dosing
No readable resultOpen on the map →What to test next →3 readable studies in this cell: 0 favour the treatment, 3 find no difference, 0 favour the comparator.
This paper's own estimate is on a different scale from the rest of the cell, so it is not drawn here.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
1 citing paper in PubMed.
- Repurposing Antidiabetic Medications for Parkinson's Disease: Focus on Biomarker Strategies for Disease Modification.International journal of molecular sciences · 2026Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The marked sentences are the ones the graph read a number from.
SummaryThis study is the first large-scale, head-to-head comparison suggesting that sodium-glucose cotransporter-2 inhibitors (SGLT2is) may offer greater neuroprotection against Parkinson's disease (PD) compared to metformin in patients with type 2 diabetes mellitus (T2DM). Utilizing a 20-year real-world dataset and propensity score matching, we found that SGLT2i users had a 28% lower adjusted hazard ratio (aHR) for PD (0.72; 95% CI, 0.62-0.84) and reduced all-cause mortality. Unlike previous studies suggesting a potential increased PD risk with SGLT2is, our robust study design, stringent exclusion criteria, and competing risk adjustments support a protective association. The findings highlight the need for further prospective research to explore the neuroprotective benefits of SGLT2is, which may justify prioritizing their use in T2DM patients at risk for neurodegeneration.BackgroundType 2 diabetes mellitus (T2DM) is linked to an increased risk of Parkinson's disease (PD), likely mediated by insulin resistance, inflammation, and mitochondrial dysfunction. While metformin has shown neuroprotective effects, sodium-glucose cotransporter-2 inhibitors (SGLT2is) have emerging benefits in neurodegeneration. This study provides the first real-world head-to-head comparison of SGLT2is and metformin on PD risk in T2DM patients.MethodsUsing the TriNetX platform, we analyzed a 20-year dataset (2005-2025) from 142 healthcare organizations, identifying 913,428 T2DM patients (96,018 SGLT2i, 817,410 metformin users). Patients with prior PD, neurodegenerative diseases, or exposure to neuroprotective/neurotoxic antidiabetic drugs were excluded. Propensity score matching (1:1) balanced cohorts across demographic, clinical, and pharmacological variables. Cox proportional hazards models estimated adjusted hazard ratios (aHRs), validated by positive and negative controls.ResultsSGLT2i use was associated with a 28% lower PD risk than metformin (aHR = 0.72; 95% CI, 0.62-0.84; p < 0.0001). Dementia, a positive control, also showed reduced risk (aHR = 0.73; 95% CI, 0.68-0.78; p < 0.0001), reinforcing the neuroprotective effect. Negative controls confirmed specificity. SGLT2i users had significantly lower all-cause mortality (aHR = 0.85; 95% CI, 0.83-0.89; p < 0.0001).ConclusionsThis first large-scale comparison suggests SGLT2is provide superior neuroprotection against PD compared to metformin in T2DM patients, warranting further investigation.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.