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Causal inference in medical records and complementary systems pharmacology for metformin drug repurposing towards dementia
Charpignon ML, Vakulenko-Lagun B, Zheng B, Magdamo C, Su B, Evans K, Rodriguez S, Sokolov A et al.. Nature communications, 2022-12-10
Topic: Drug trials: efficacy and safety
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.
Key findings
- Mixed results are emerging from prior observational studies.
- 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.
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Study details
- Evidence strengthLow
How this study scored 47/100
Published in a leading specialty journal. Scored zero for study design, sample size, effect reported, studied in people and randomised / blinded because the record does not state it. We have no data on journal's citation record, times cited, citations per year, impact for its field and year, cited by studies here, still being cited, senior author's track record, institution's track record and multi-centre collaboration, so those were left out: it earned 27 of the 58 points we could judge it on, which is 47 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (Nature communications) |
| Journal's citation record | — / 4 | No journal record from OpenAlex — left out of this score |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 1 / 5 | Rated “low” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 3 / 5 | 2022 — within 6 year(s) of the newest study here |
| Sample size | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 0 / 3 | Not stated whether this was studied in people — scores zero (not stated in the record — scored 0) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | — / 7 | No citation count (not found in OpenAlex) — left out of this score |
| Citations per year | — / 5 | No citation count or no year — left out of this score |
| Impact for its field and year | — / 6 | No field-weighted citation impact (OpenAlex has none yet) — left out of this score |
| Cited by studies here | — / 6 | Not yet checked against this library's citation graph — left out of this score |
| Still being cited | — / 4 | No yearly citation counts — left out of this score |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | — / 3 | No institution listed in OpenAlex — left out of this score |
| Multi-centre collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 36496454) |
| Free to read | 2 / 2 | Free to read |
| Points | 27 / 58 | Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 27 of the 58 points we could judge it on is 47 out of 100. |
| Total | 47 / 100 | — |
What each of these 20 components measures, and what this score is not →
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APA 7th
Charpignon, M. L., Vakulenko-Lagun, B., Zheng, B., Magdamo, C., Su, B., Evans, K., et al. (2022). Causal inference in medical records and complementary systems pharmacology for metformin drug repurposing towards dementia. Nature communications. https://doi.org/10.1038/s41467-022-35157-w
Vancouver
Charpignon ML, Vakulenko-Lagun B, Zheng B, Magdamo C, Su B, Evans K, et al. Causal inference in medical records and complementary systems pharmacology for metformin drug repurposing towards dementia. Nature communications. 2022. doi:10.1038/s41467-022-35157-w. PMID: 36496454.
BibTeX
@article{charpignon2022-36496454,
author = {Charpignon, M. L. and Vakulenko-Lagun, B. and Zheng, B. and Magdamo, C. and Su, B. and Evans, K. and Rodriguez, S. and Sokolov, A. and others},
title = {{Causal inference in medical records and complementary systems pharmacology for metformin drug repurposing towards dementia}},
journal = {Nature communications},
year = {2022},
doi = {10.1038/s41467-022-35157-w},
pmid = {36496454},
url = {https://doi.org/10.1038/s41467-022-35157-w}
}