Evidence map›Insulin × glycemic control›PMID 42064764›Full record

SynthesisFrontiers in endocrinology2026

The impact of antidiabetic drugs on dementia risk: a Bayesian network meta-analysis.

Yang Yu, Xu Peng, Chang Su, Yangguang Bai, Dan Hou

Abstract readNetwork Meta-AnalysisSystematic Review
PubMed Full text at PMC Publisher
In one paragraph

Synthesis in Frontiers in endocrinology, 2026. The graph read 5 numbers from its abstract, feeding 3 cells of the map, but none could be read as for or against, so it casts no vote. Not yet cited in PubMed.

5numbers the graph read from it
0cells of the map it votes in
0citing 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.

Read, but not usablea number the graph found but could not read as for or against

Glycemic controldirection of benefit for this outcome is not defined · head-to-head · t2dfeeds 3 cells of the map
OR 0.790.77 to 0.81
Results: A total of 28 articles (involving 4,382,897 patients), network meta-analysis results indicates that compared with placebo, Insulin [OR = 0.11, 95% CrI (0.1, 0.12)], Metformin [OR = 0.79, 95% CrI (0.77, 0.81)], and Pioglitazone [OR = 0.69, 95% CrI (0.56, 0.86)] all reduced the incidence of dementia compared to placebo, a higher incidence of Alzheimer's dementia[OR = 1.78, 95% CrI (1.66, 1.91)] and Vascular dementia[OR = 2.59, 95% CrI (2.33, 2.88)] with DPP4i compared to SGLT_2i.
FeedsInsulin×glycemic controlMetformin×glycemic controlThiazolidinediones×glycemic control
Glycemic controldirection of benefit for this outcome is not defined · head-to-head · t2dfeeds 3 cells of the map
OR 0.690.56 to 0.86
Results: A total of 28 articles (involving 4,382,897 patients), network meta-analysis results indicates that compared with placebo, Insulin [OR = 0.11, 95% CrI (0.1, 0.12)], Metformin [OR = 0.79, 95% CrI (0.77, 0.81)], and Pioglitazone [OR = 0.69, 95% CrI (0.56, 0.86)] all reduced the incidence of dementia compared to placebo, a higher incidence of Alzheimer's dementia[OR = 1.78, 95% CrI (1.66, 1.91)] and Vascular dementia[OR = 2.59, 95% CrI (2.33, 2.88)] with DPP4i compared to SGLT_2i.
FeedsInsulin×glycemic controlMetformin×glycemic controlThiazolidinediones×glycemic control
Glycemic controldirection of benefit for this outcome is not defined · head-to-head · t2dfeeds 3 cells of the map
OR 0.110.10 to 0.12
Results: A total of 28 articles (involving 4,382,897 patients), network meta-analysis results indicates that compared with placebo, Insulin [OR = 0.11, 95% CrI (0.1, 0.12)], Metformin [OR = 0.79, 95% CrI (0.77, 0.81)], and Pioglitazone [OR = 0.69, 95% CrI (0.56, 0.86)] all reduced the incidence of dementia compared to placebo, a higher incidence of Alzheimer's dementia[OR = 1.78, 95% CrI (1.66, 1.91)] and Vascular dementia[OR = 2.59, 95% CrI (2.33, 2.88)] with DPP4i compared to SGLT_2i.
FeedsInsulin×glycemic controlMetformin×glycemic controlThiazolidinediones×glycemic control
Glycemic controldirection of benefit for this outcome is not defined · head-to-head · t2dfeeds 3 cells of the map
OR 2.592.33 to 2.88
Results: A total of 28 articles (involving 4,382,897 patients), network meta-analysis results indicates that compared with placebo, Insulin [OR = 0.11, 95% CrI (0.1, 0.12)], Metformin [OR = 0.79, 95% CrI (0.77, 0.81)], and Pioglitazone [OR = 0.69, 95% CrI (0.56, 0.86)] all reduced the incidence of dementia compared to placebo, a higher incidence of Alzheimer's dementia[OR = 1.78, 95% CrI (1.66, 1.91)] and Vascular dementia[OR = 2.59, 95% CrI (2.33, 2.88)] with DPP4i compared to SGLT_2i.
FeedsInsulin×glycemic controlMetformin×glycemic controlThiazolidinediones×glycemic control
Glycemic controldirection of benefit for this outcome is not defined · head-to-head · t2dfeeds 3 cells of the map
OR 1.781.66 to 1.91
Results: A total of 28 articles (involving 4,382,897 patients), network meta-analysis results indicates that compared with placebo, Insulin [OR = 0.11, 95% CrI (0.1, 0.12)], Metformin [OR = 0.79, 95% CrI (0.77, 0.81)], and Pioglitazone [OR = 0.69, 95% CrI (0.56, 0.86)] all reduced the incidence of dementia compared to placebo, a higher incidence of Alzheimer's dementia[OR = 1.78, 95% CrI (1.66, 1.91)] and Vascular dementia[OR = 2.59, 95% CrI (2.33, 2.88)] with DPP4i compared to SGLT_2i.
FeedsInsulin×glycemic controlMetformin×glycemic controlThiazolidinediones×glycemic control

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.

Insulin×glycemic control

No readable resultOpen on the map →What to test next →

40 readable studies in this cell: 15 favour the treatment, 14 find no difference, 14 favour the comparator.

Belief with this paper
0.50contested · 9 families support, 6 contradict · against placebo
Without itNot a counted family in this claim, so removing it changes nothing.
← favours the comparatorfavours the treatment →
0 · no effect
NCT036893742,274 enrolled · 2018
Δ -0.29-0.38 to -0.20
NCT037306622,002 enrolled · 2018
Δ -0.99-1.13 to -0.86
NCT013360231,663 enrolled · 2011
Treatment contrast -0.64-0.75 to -0.53
NCT038829701,444 enrolled · 2019
Δ -0.86-1.00 to -0.72
NCT045379231,428 enrolled · 2020
Δ -1.10-1.24 to -0.97
NCT032680051,264 enrolled · 2017
Δ -0.04-0.11 to 0.03
NCT020581471,170 enrolled · 2014
Δ -0.78-0.90 to -0.67
NCT021289321,089 enrolled · 2014
Δ -0.81-0.96 to -0.67
NCT009606611,036 enrolled · 2009
Δ -0.04-0.18 to 0.11
NCT00856986987 enrolled · 2009
Δ -0.52-0.68 to -0.36
NCT01117350978 enrolled · 2010
Δ 2.54-3.88 to 8.93
NCT03214380933 enrolled · 2017
Δ 0.06-0.05 to 0.16

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

Metformin×glycemic control

No readable resultOpen on the map →What to test next →

40 readable studies in this cell: 41 favour the treatment, 13 find no difference, 7 favour the comparator.

Belief with this paper
0.84replicated · 32 families support, 6 contradict · against placebo
Without itNot a counted family in this claim, so removing it changes nothing.
← favours the treatmentfavours the comparator →
0 · no effect
NCT017190031,413 enrolled · 2012
Adjusted mean -0.72-0.95 to -0.48
NCT018093271,186 enrolled · 2013
Δ -0.40-0.59 to -0.21
NCT022730501,136 enrolled · 2014
Δ -0.89-1.08 to -0.69
NCT008598981,093 enrolled · 2009
Δ -0.53-0.74 to -0.32
The study to understand the genetics of the acute response to metformi…PMID 25812009 · 1,033 enrolled · 2008
Δ -0.85-43.8 to 26.7
NCT00643851994 enrolled · 2008
Δ -0.86-1.11 to -0.62
NCT01708902876 enrolled · 2012
Δ -1.00-1.23 to -0.78
NCT00676338820 enrolled · 2008
Δ -0.05-0.26 to 0.17
NCT01126580807 enrolled · 2010
Δ -0.22-0.36 to -0.08
NCT01023581784 enrolled · 2009
Δ -0.67-0.96 to -0.37
NCT01076088744 enrolled · 2010
Δ -0.84-1.15 to -0.52
NCT00386100688 enrolled · 2006
Δ -0.49-0.67 to -0.30

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

Thiazolidinediones×glycemic control

No readable resultOpen on the map →What to test next →

16 readable studies in this cell: 9 favour the treatment, 4 find no difference, 3 favour the comparator.

Belief with this paper
0.83established · 5 families support, 1 contradict · against placebo
Without itNot a counted family in this claim, so removing it changes nothing.
← favours the comparatorfavours the treatment →
0 · no effect
NCT00676338820 enrolled · 2008
Δ 0.10-0.15 to 0.35
NCT00839527685 enrolled · 2009
Δ 0.250.10 to 0.40
NCT00727857600 enrolled · 2007
Δ 0.840.50 to 1.18
NCT01076075427 enrolled · 2010
Δ -0.68-0.87 to -0.50
NCT00770653305 enrolled · 2007
Δ 0.16-0.02 to 0.33
NCT0158944577 enrolled · 2008
Δ -0.74-7.90 to 8.00
NCT0031865623 enrolled · 2005
Δ 5.02-0.32 to 10.4
Rosiglitazone treatment increases subcutaneous adipose tissue glucose …PMID 16189256 · 2005
decrease -18.0
Efficacy and safety of adding pioglitazone or sitagliptin to patients …PMID 23807528
Δ 5.70
Glycemic control with glyburide/metformin tablets in combination with …PMID 14969649 · 2004
Δ -48.0
Efficacy and Safety of High-Dose Pioglitazone as Add-on Therapy in Pat…PMID 41151541 · 2026
Δ -0.80
Free fatty acid kinetics during long-term treatment with pioglitazone …PMID 19298459 · 2009
Δ -0.11

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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

5 authors.

Yang YuDepartment of Radiation Oncology, The First Hospital of Jilin University, Changchun, China.
Xu PengDepartment of Pathology and Lab Medicine, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China.
Chang SuCollege of Pharmacy, Dalian Medical University, Dalian, China.
Yangguang BaiDepartment of Pharmacy and Shandong Provincial Key Traditional Chinese Medical Discipline of Clinical Chinese Pharmacy, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China.
Dan HouDepartment of Pharmacy and Shandong Provincial Key Traditional Chinese Medical Discipline of Clinical Chinese Pharmacy, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China.

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.

Background: Diabetes is significantly associated with cognitive impairment, particularly the risk of developing dementia. However, the impact of antidiabetic drugs on dementia risk remains unclear. This study aims to comprehensively evaluate the effects of different antidiabetic drugs on dementia risk using Bayesian network analysis. Methods: The study systematically searched databases including PubMed, Embase, and the Cochrane Library to identify relevant publications up to September 5, 2025. Eligible randomized controlled trials, cohort studies, and case-control studies were selected. We employed a Bayesian network meta-analysis model to quantitatively assess the relationship between antidiabetic drugs and dementia risk. Data analysis was performed using R version 4.4.1. Results: A total of 28 articles (involving 4,382,897 patients), network meta-analysis results indicates that compared with placebo, Insulin [OR = 0.11, 95% CrI (0.1, 0.12)], Metformin [OR = 0.79, 95% CrI (0.77, 0.81)], and Pioglitazone [OR = 0.69, 95% CrI (0.56, 0.86)] all reduced the incidence of dementia compared to placebo, a higher incidence of Alzheimer's dementia[OR = 1.78, 95% CrI (1.66, 1.91)] and Vascular dementia[OR = 2.59, 95% CrI (2.33, 2.88)] with DPP4i compared to SGLT_2i. Conclusion: This study indicate that insulin demonstrates the most pronounced efficacy in reducing the incidence risk of dementia and vascular dementia. Furthermore, SGLT_2i and GLP1 exhibit certain therapeutic benefits in the management of Alzheimer's disease. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD420251172386.

Indexed as

DementiaDiabetes Mellitus, Type 2Hypoglycemic AgentsBayes TheoremHumansInsulinMetforminPioglitazoneRisk FactorsHypoglycemic AgentsInsulinMetforminPioglitazoneAlzheimer’s diseaseantidiabetic drugsBayesian network analysisdementia riskmeta-analysissystematic review

Identifiers

PMID42064764
PMCPMC13124527

What Socratic holds

Texttitle and abstract
LicenceCC BY
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.