Observational studyCardiovascular diabetology2018

Glitazones and alpha-glucosidase inhibitors as the second-line oral anti-diabetic agents added to metformin reduce cardiovascular risk in Type 2 diabetes patients: a nationwide cohort observational study.

Cheng-Wei Chan, Chu-Leng Yu, Jiunn-Cherng Lin, Yu-Cheng Hsieh, Che-Chen Lin, Chen-Ying Hung, Cheng-Hung Li, Ying-Chieh Liao, Chu-Pin Lo, Jin-Long Huang and 2 more

Full text readComparative StudyObservational Study
In one paragraph

Observational study in Cardiovascular diabetology, 2018. The graph read 2 numbers from its abstract, feeding 2 cells of the map: it supports the treatment in 1. Cited by 28 papers, 3 of them syntheses that pooled it.

2numbers the graph read from it
2cells of the map it votes in
28citing papers in PubMed, 3 pooled it
–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 →
0.51 · no effect
Cardiovascular eventsfavours the treatment · head-to-head · ascvd, t2dfeeds 2 cells of the map
HR 0.660.50 to 0.88p = 0.004
Compared with the SU+metformin group (reference), the TZD+metformin (adjusted HR: 0.66; 95% CI 0.50-0.88, p = 0.004) and AGI+metformin (adjusted HR: 0.74; 95% CI 0.59-0.94, p = 0.01) groups showed a significantly lower risk of MACE.
Cardiovascular eventsfavours the treatment · head-to-head · ascvd, t2dfeeds 2 cells of the map
HR 0.740.59 to 0.94p = 0.01
Compared with the SU+metformin group (reference), the TZD+metformin (adjusted HR: 0.66; 95% CI 0.50-0.88, p = 0.004) and AGI+metformin (adjusted HR: 0.74; 95% CI 0.59-0.94, p = 0.01) groups showed a significantly lower risk of MACE.

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.

Metformin×cardiovascular events

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

5 readable studies in this cell: 4 favour the treatment, 1 find no difference, 0 favour the comparator.

Belief with this paper
0.50contested · 4 families support, 2 contradict · against placebo
Without itNot a counted family in this claim, so removing it changes nothing.
← favours the treatmentfavours the comparator →
1 · no effect

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

Thiazolidinediones×cardiovascular events

SupportsOpen on the map →What to test next →

1 readable study in this cell: 0 favour the treatment, 1 find no difference, 0 favour the comparator.

Belief with this paper
0.25no deciding trial · 0 families support, 0 contradict · head-to-head
Without itNot a counted family in this claim, so removing it changes nothing.
← favours the treatmentfavours the comparator →
0 · no effect
NCT00770653305 enrolled · 2007
Δ -367-964 to 230

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

28 citing papers in PubMed, 3 syntheses or guidelines pooled it.

  1. Pooled it
  2. Pooled it
  3. Pooled it
  4. Trial
  5. Review
  6. Review
  7. Association between trabecular bone score and cardiovascular outcomes: a population-level historical cohort study.Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA · 2026
    Article
  8. Article
  9. Article
  10. Article
  11. FRAX predicts cardiovascular risk in women undergoing osteoporosis screening: the Manitoba bone mineral density registry.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2024
    Article
  12. Review
  13. Review
  14. Article
  15. Observational
  16. The Mechanisms of the Development of Atherosclerosis in Prediabetes.International journal of molecular sciences · 2021
    Review
  17. Article
  18. Observational
  19. Article
  20. Observational
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

12 authors.

Cheng-Wei ChanCardiovascular Center, Taichung Veterans General Hospital, Taichung, Taiwan.
Chu-Leng YuCardiovascular Center, Taichung Veterans General Hospital, Taichung, Taiwan.
Jiunn-Cherng LinCardiovascular Center, Taichung Veterans General Hospital, Taichung, Taiwan.
Yu-Cheng HsiehCardiovascular Center, Taichung Veterans General Hospital, Taichung, Taiwan. ychsieh@vghtc.gov.tw.ORCID http://orcid.org/0000-0001-6218-7139
Che-Chen LinDepartment of Medical Research, Taichung Veterans General Hospital, Taichung, Taiwan.
Chen-Ying HungDepartment of Internal Medicine, Hsinchu Branch, Taipei Veterans General Hospital, Hsinchu, Taiwan.
Cheng-Hung LiCardiovascular Center, Taichung Veterans General Hospital, Taichung, Taiwan.
Ying-Chieh LiaoCardiovascular Center, Taichung Veterans General Hospital, Taichung, Taiwan.
Chu-Pin LoDepartment of Financial and Computational Mathematics, Providence University, Taichung, Taiwan.
Jin-Long HuangCardiovascular Center, Taichung Veterans General Hospital, Taichung, Taiwan.
Ching-Heng LinDepartment of Medical Research, Taichung Veterans General Hospital, Taichung, Taiwan.
Tsu-Juey WuCardiovascular Center, Taichung Veterans General Hospital, Taichung, Taiwan.

Funding

National Science Council, Taiwan 102-2314-B-075A-009-MY2National Science Council, Taiwan 104-2314-B-367-001National Science Council, Taiwan 105-2314-B-367-001-MY3Taichung Veterans General Hospital TCVGH-1033103CTaichung Veterans General Hospital TCVGH-1033105CTaichung Veterans General Hospital TCVGH-1043109CTaichung Veterans General Hospital TCVGH-1053108CTaichung Veterans General Hospital TCVGH-1067310CTaichung Veterans General Hospital TCVGH-FCU1068205Taichung Veterans General Hospital TCVGH-NHRI10603Taichung Veterans General Hospital TCVGH-VHCY1068606Taichung Veterans General Hospital TCVGH-VTA106PREM1Taichung Veterans General Hospital TCVGH-YM1060201
8 · The paper itself

Abstract

The marked sentences are the ones the graph read a number from.

objectiveMetformin is the standard first-line drug for patients with Type 2 diabetes (T2DM). However, the optimal second-line oral anti-diabetic agent (ADA) remains unclear. We investigated the cardiovascular risk of various ADAs used as add-on medication to metformin in T2DM patients from a nationwide cohort.

methodsT2DM patients using different add-on oral ADAs after an initial metformin therapy of > 90 days were identified from the Taiwan National Health Insurance Database. Five classes of ADAs, including sulphonylureas (SU), glinides, thiazolidinediones (TZD), alpha-glucosidase inhibitors (AGI), and dipeptidyl peptidase-4 inhibitors (DPP-4I) were selected for analysis. The reference group was the SU added to metformin. Patients were excluded if aged < 20 years, had a history of stroke or acute coronary syndrome (ACS), or were receiving insulin treatment. The primary outcomes included any major adverse cardiovascular event (MACE) including ACS, ischemic/hemorrhagic stroke, and death. A Cox regression model was used to estimate the hazard ratio (HR) for MACE.

resultsA total of 26,742 patients receiving their add-on drug to metformin of either SU (n = 24,277), glinides (n = 962), TZD (n = 581), AGI (n = 808), or DPP-4I (n = 114) were analyzed. After a mean follow-up duration of 6.6 ± 3.4 years, a total of 4775 MACEs occurred. Compared with the SU+metformin group (reference), the TZD+metformin (adjusted HR: 0.66; 95% CI 0.50-0.88, p = 0.004) and AGI+metformin (adjusted HR: 0.74; 95% CI 0.59-0.94, p = 0.01) groups showed a significantly lower risk of MACE.

conclusionBoth TZD and AGI, when used as an add-on drug to metformin were associated with lower MACE risk when compared with SU added to metformin in this retrospective cohort study. Trial registration CE13152B-3. Registered 7 Mar, 2013, retrospectively registered.

Indexed as

Administration, OralAdultAgedCardiovascular DiseasesDatabases, FactualDiabetes Mellitus, Type 2Drug Therapy, CombinationFemaleGlycoside Hydrolase InhibitorsHumansHypoglycemic AgentsMaleMetforminMiddle AgedRetrospective StudiesRisk AssessmentGlycoside Hydrolase InhibitorsHypoglycemic AgentsMetforminThiazolidinedionesAnti-diabetic agentCardiovascular riskMetforminType 2 diabetes

Identifiers

PMID29368615
PMCPMC5781294

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Registered trials

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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.