ArticleNature communications2022
Causal inference in medical records and complementary systems pharmacology for metformin drug repurposing towards dementia.
Article in Nature communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers, 1 of them a synthesis that pooled 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.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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
30 citing papers in PubMed, 1 synthesis or guideline pooled it, 46 citations in OpenAlex.
- Pooled it
- Effect of Metformin on Plasma and Cerebrospinal Fluid Biomarkers in Non-Diabetic Older Adults with Mild Cognitive Impairment Related to Alzheimer's Disease.Journal of Alzheimer's disease : JAD · 2024Trial
- Delirium and Increased Risk of Developing Dementia: An Emulated Target Trial Analysis.medRxiv : the preprint server for health sciences · 2026Article
- From Molecular Networks to Medicines: Targeting Complexity in Alzheimer's Disease (AD) Therapy.Molecular neurobiology · 2026Review
- Causal inference in real-world dementia research: a systematic review protocol.Systematic reviews · 2026Article
- Ferroptosis in Spine-Related Diseases: Mechanistic Insights and Potential Therapeutic Targets.Cellular and molecular neurobiology · 2026Review
- Artificial intelligence and machine learning for precision prevention of cognitive decline: integrating multimodal biomarkers, lifestyle interventions, and natural medicines from prediction to clinical practice.Frontiers in aging neuroscience · 2026Review
- A Deep Subgrouping Framework for Precision Drug Repurposing via Emulating Clinical Trials on Real-world Patient Data.KDD : proceedings. International Conference on Knowledge Discovery & Data Mining · 2025Article
- Federated target trial emulation using distributed observational data for treatment effect estimation.NPJ digital medicine · 2025Article
- Comparative Effectiveness of Metformin Versus Sulfonylureas on Exceptional Longevity in Women With Type 2 Diabetes: Target Trial Emulation.The journals of gerontology. Series A, Biological sciences and medical sciences · 2025Article
- Computational Drug Repositioning in Cardiorenal Disease: Opportunities, Challenges, and Approaches.Proteomics · 2025Article
- Federated Target Trial Emulation using Distributed Observational Data for Treatment Effect Estimation.medRxiv : the preprint server for health sciences · 2025Article
- Investigating Primary Care Indications to Improve the Quality of Electronic Health Record Data in Target Trial Emulation for Dementia.medRxiv : the preprint server for health sciences · 2025Article
- Review
- An open-source framework for end-to-end analysis of electronic health record data.Nature medicine · 2024Article
- Latent profile analysis reveals overlapping ARFID and shape/weight motivations for restriction in eating disorders.Psychological medicine · 2024Article
- Integration of National Health Insurance claims data and animal models reveals fexofenadine as a promising repurposed drug for Parkinson's disease.Journal of neuroinflammation · 2024Article
- Repurposing of Antidiarrheal Loperamide for Treating Melanoma by Inducing Cell Apoptosis and Cell Metastasis SuppressionCurrent cancer drug targets · 2024Article
- Sildenafil as a Candidate Drug for Alzheimer's Disease: Real-World Patient Data Observation and Mechanistic Observations from Patient-Induced Pluripotent Stem Cell-Derived Neurons.Journal of Alzheimer's disease : JAD · 2024Article
- Dementia risk analysis using temporal event modeling on a large real-world dataset.Scientific reports · 2023Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
20 authors at 9 institutions in 4 countries.
Funding
Abstract
Metformin, a diabetes drug with anti-aging cellular responses, has complex actions that may alter dementia onset. Mixed results are emerging from prior observational studies. To address this complexity, we deploy a causal inference approach accounting for the competing risk of death in emulated clinical trials using two distinct electronic health record systems. In intention-to-treat analyses, metformin use associates with lower hazard of all-cause mortality and lower cause-specific hazard of dementia onset, after accounting for prolonged survival, relative to sulfonylureas. In parallel systems pharmacology studies, the expression of two AD-related proteins, APOE and SPP1, was suppressed by pharmacologic concentrations of metformin in differentiated human neural cells, relative to a sulfonylurea. Together, our findings suggest that metformin might reduce the risk of dementia in diabetes patients through mechanisms beyond glycemic control, and that SPP1 is a candidate biomarker for metformin's action in the brain.
Indexed as
Identifiers
What OpenQuestion holds
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 OpenQuestion graph.