Observational studyJournal of Parkinson's disease2025

SGLT2 inhibitors vs. metformin for Parkinson's disease risk reduction in type 2 diabetes.

Mingyang Sun, Xiaoling Wang, Zhongyuan Lu, Yitian Yang, Shuang Lv, Mengrong Miao, Wan-Ming Chen, Szu-Yuan Wu, Jiaqiang Zhang

Abstract readComparative StudyObservational StudyComparative Study
In one paragraph

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.

2numbers the graph read from it
1cell of the map it votes in
1citing papers in PubMed
field-weighted citation impact
1 · What the graph read from it

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.

← favours the treatmentfavours the comparator →
1 · no effect
All-cause mortalitySGLT2i vs metforminfavours the treatment · t2dfeeds one cell of the map
HR 0.850.83 to 0.89p < 0.0001
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

PDSGLT2i vs metformindirection of benefit for this outcome is not defined · t2dfeeds one cell of the map
HR 0.720.62 to 0.84p < 0.0001
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).

clause the extractor read what became the number

2 · Its place on the map

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.

supports the treatmentfavours the comparatorno clear differenceread, but no usable result
3 · What it changes

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.

Belief with this paper
0.50contested · 5 families support, 4 contradict · against placebo
Without itNot a counted family in this claim, so removing it changes nothing.
← favours the comparatorfavours the treatment →
1 · no effect
NCT0546531762,197 enrolled · 2022
HR 0.750.65 to 0.86
NCT0399313226,774 enrolled · 2018
HR 0.990.83 to 1.18
NCT0173053417,190 enrolled · 2013
HR 0.930.84 to 1.03
NCT045096746,522 enrolled · 2020
HR 0.900.76 to 1.06
NCT036192136,263 enrolled · 2018
HR 0.820.73 to 0.92
NCT030579515,988 enrolled · 2017
HR 0.790.69 to 0.90
NCT019897545,813 enrolled · 2014
HR 0.720.55 to 0.94
NCT020657914,401 enrolled · 2014
HR 0.700.59 to 0.82
NCT010326294,330 enrolled · 2009
HR 0.930.78 to 1.12
NCT030579773,730 enrolled · 2017
HR 0.750.65 to 0.86
NCT043636972,401 enrolled · 2020
HR 0.860.68 to 1.08
NCT04157751530 enrolled · 2020
Stratified Win Ratio 1.361.09 to 1.68

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.

Belief with this paper
0.00contested · 0 families support, 1 contradict · against placebo
Without itNot a counted family in this claim, so removing it changes nothing.
← favours the treatmentfavours the comparator →
0 · no effect
NCT02532855614 enrolled · 2015
Δ -4.40-10.1 to 1.40
NCT0333885526 enrolled · 2018
Δ -244-590 to 101

This paper's own estimate is on a different scale from the rest of the cell, so it is not drawn here.

4 · The registry

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.

5 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Review
6 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

7 · Who and what money

Authors and funding

9 authors.

Mingyang SunDepartment of Anesthesiology and Perioperative Medicine, People's Hospital of Zhengzhou University, Henan Provincial People's Hospital, Zhengzhou, China.
Xiaoling WangDepartment of Anesthesiology and Perioperative Medicine, People's Hospital of Zhengzhou University, Henan Provincial People's Hospital, Zhengzhou, China.
Zhongyuan LuDepartment of Anesthesiology and Perioperative Medicine, People's Hospital of Zhengzhou University, Henan Provincial People's Hospital, Zhengzhou, China.
Yitian YangDepartment of Anesthesiology and Perioperative Medicine, People's Hospital of Zhengzhou University, Henan Provincial People's Hospital, Zhengzhou, China.
Shuang LvDepartment of Anesthesiology and Perioperative Medicine, People's Hospital of Zhengzhou University, Henan Provincial People's Hospital, Zhengzhou, China.
Mengrong MiaoDepartment of Anesthesiology and Perioperative Medicine, People's Hospital of Zhengzhou University, Henan Provincial People's Hospital, Zhengzhou, China.
Wan-Ming ChenGraduate Institute of Business Administration, College of Management, Fu Jen Catholic University, Taipei, Taiwan.
Szu-Yuan WuGraduate Institute of Business Administration, College of Management, Fu Jen Catholic University, Taipei, Taiwan.
Jiaqiang ZhangDepartment of Anesthesiology and Perioperative Medicine, People's Hospital of Zhengzhou University, Henan Provincial People's Hospital, Zhengzhou, China.ORCID 0000-0002-1367-9644

Funding

No grant is acknowledged in the PubMed record.

8 · The paper itself

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.

Indexed as

Diabetes Mellitus, Type 2Hypoglycemic AgentsMetforminNeuroprotective AgentsParkinson DiseaseSodium-Glucose Transporter 2 InhibitorsAgedDatasets as TopicFemaleHumansMaleMiddle AgedPropensity ScoreProportional Hazards ModelsHypoglycemic AgentsMetforminNeuroprotective AgentsSodium-Glucose Transporter 2 Inhibitorsmetforminparkinson's diseasereal-world studysodium-glucose cotransporter-2 inhibitorstype 2 diabetes mellitus

Identifiers

PMID40671477
PMCPMC13347531

What Socratic holds

Texttitle and abstract
LicenceCC BY-NC
Read underepoch 390

Registered trials

None linked

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.