SynthesisAmerican journal of cardiovascular drugs : drugs, devices, and other interventions2024

Evaluation of the Lifetime Benefits of Metformin and SGLT2 Inhibitors in Type 2 Diabetes Mellitus Patients with Cardiovascular Disease: A Systematic Review and Two-Stage Meta-Analysis.

Hon Jen Wong, Norman H Lin, Yao Neng Teo, Nicholas L Syn, Yao Hao Teo, Ching-Hui Sia

Abstract readSystematic ReviewMeta-Analysis
PubMed Publisher
In one paragraph

Synthesis in American journal of cardiovascular drugs : drugs, devices, and other interventions, 2024. The graph read 1 number from its abstract, feeding 2 cells of the map, but none could be read as for or against, so it casts no vote. Cited by 3 papers.

1number the graph read from it
0cells of the map it votes in
3citing 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

All-cause mortalitycomparator not stated · ascvd, t2dfeeds 2 cells of the map
HR 1.311.10 to 1.55
However, participants receiving SGLT2 inhibitors had a higher all-cause mortality (hazard ratio 1.308, 95% confidence interval 1.103-1.550) versus metformin.

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×all-cause mortality

No readable resultOpen 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
0.50one trial · 1 family supports, 0 contradict · against placebo
Without itNot a counted family in this claim, so removing it changes nothing.
← favours the treatmentfavours the comparator →
1 · no effect
NCT000387272,779 enrolled · 1996
HR 0.990.79 to 1.25

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

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.

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

3 citing papers in PubMed.

  1. Metformin Beyond Glycemic Control: Cardiovascular Protection and Diabetes Prevention.Journal of cardiovascular development and disease · 2026
    Review
  2. Article
  3. Article
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

6 authors.

Hon Jen Wong *Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
Norman H Lin *Department of Cardiology, National University Heart Centre Singapore, 1E Kent Ridge Road, NUHS Tower Block Level 9, Singapore, 119228, Singapore.
Yao Neng TeoYong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
Nicholas L SynDepartment of Cardiology, National University Heart Centre Singapore, 1E Kent Ridge Road, NUHS Tower Block Level 9, Singapore, 119228, Singapore.
Yao Hao TeoDepartment of Cardiology, National University Heart Centre Singapore, 1E Kent Ridge Road, NUHS Tower Block Level 9, Singapore, 119228, Singapore.
Ching-Hui SiaYong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore. ching_hui_sia@nuhs.edu.sg.ORCID http://orcid.org/0000-0002-2764-2869

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.

backgroundMetformin and sodium-glucose cotransporter-2 (SGLT2) inhibitors have demonstrated cardiovascular benefits but their comparative effects on mortality in type 2 diabetes mellitus (T2DM) patients with cardiovascular disease (CVD) are unknown. Hence, we evaluated and compared lifetime benefits arising from metformin or SGLT2 inhibitors in T2DM patients with CVD. MATERIALS AND

methodsStudies published in the PubMed, EMBASE and CENTRAL databases before 28 October 2023 were retrieved. Treatment effects of metformin against US FDA-approved SGLT2 inhibitors in T2DM patients with CVD were evaluated and lifetime gains in event-free survival were estimated from our primary endpoints of all-cause and cardiovascular mortality. Risk ratios were derived to assess their impact on secondary outcomes such as major adverse cardiovascular events and hospitalizations for heart failure.

resultsOverall, 14 studies were included. Five studies published Kaplan-Meier curves for the primary outcome of all-cause mortality. Individual participant data were reconstructed from these Kaplan-Meier curves, from which we conducted our two-stage meta-analysis. Participants receiving metformin and SGLT2 inhibitors experienced a reduction in the risk for all-cause mortality as compared with those not taking metformin and placebo. However, participants receiving SGLT2 inhibitors had a higher all-cause mortality (hazard ratio 1.308, 95% confidence interval 1.103-1.550) versus metformin. Treatment with metformin was estimated to offer an additional 23.26 months of survival free from all-cause mortality versus 23.04 months with SGLT2 inhibitors.

conclusionsIn patients with T2DM and CVD, metformin and SGLT2 inhibitors were associated with substantially lower all-cause mortality rates and slightly longer life expectancies than in patients without. Metformin presented an advantage over SGLT2 inhibitors in reducing all-cause mortality.

Indexed as

Cardiovascular DiseasesDiabetes Mellitus, Type 2Hypoglycemic AgentsMetforminSodium-Glucose Transporter 2 InhibitorsHumansHypoglycemic AgentsMetforminSodium-Glucose Transporter 2 Inhibitors

Identifiers

What Socratic holds

Texttitle and abstract
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.