SynthesisEuropean journal of medical research2025

Comparative efficacy of GLP-1 RAs/SGLT-2 inhibitors in reducing cardiovascular events in type 2 diabetes according to baseline use of metformin: a systematic review and meta-analysis of randomized controlled trials.

Yuxin Zhang, Zhaoji Li, Yongchen Hao

Abstract readMeta-AnalysisSystematic ReviewComparative Study
In one paragraph

Synthesis in European journal of medical research, 2025. The graph read 1 number from its abstract, feeding 3 cells of the map: it supports the treatment in 3. Cited by 5 papers, 2 of them syntheses that pooled it.

1number the graph read from it
3cells of the map it votes in
5citing papers in PubMed, 2 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 →
1 · no effect
Cardiovascular eventsfavours the treatment · against placebo · ascvd, t2dfeeds 3 cells of the map
HR 0.950.91 to 0.99P = 0.02
Among patients using metformin at baseline, SGLT-2i or GLP-1 RAs reduced MACE risk (HR = 0.95, 95% CI 0.91-0.99, P = 0.02).

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.

GLP-1 receptor agonists×cardiovascular events

SupportsOpen on the map →What to test next →

13 readable studies in this cell: 7 favour the treatment, 2 find no difference, 4 favour the comparator.

Belief with this paper
0.50contested · 7 families support, 3 contradict · against placebo
Without itNot a counted family in this claim, so removing it changes nothing.
← favours the treatmentfavours the comparator →
1 · no effect
NCT0399313226,774 enrolled · 2018
HR 1.010.91 to 1.11
NCT0357459717,604 enrolled · 2018
HR 0.800.72 to 0.89
NCT013949529,901 enrolled · 2011
HR 0.880.79 to 0.99
NCT039143269,651 enrolled · 2019
HR 0.860.77 to 0.96
NCT011790489,341 enrolled · 2010
HR 0.870.78 to 0.97
NCT038191533,533 enrolled · 2019
HR 0.760.66 to 0.88
NCT017204463,297 enrolled · 2013
HR 0.740.58 to 0.95
NCT026927163,183 enrolled · 2017
HR 0.790.57 to 1.11
OR 1.951.28 to 3.00
NCT05564039282 enrolled · 2022
OR 20.48.40 to 49.8

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

Metformin×cardiovascular events

SupportsOpen 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.

SGLT2 inhibitors×cardiovascular events

SupportsOpen on the map →What to test next →

22 readable studies in this cell: 9 favour the treatment, 11 find no difference, 2 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 →
1 · no effect
NCT0546531762,197 enrolled · 2022
HR 0.750.65 to 0.86
NCT0399313226,774 enrolled · 2018
HR 1.010.91 to 1.11
NCT0173053417,190 enrolled · 2013
HR 0.930.84 to 1.03
NCT0493781616,746 enrolled · 2021
HR 1.000.83 to 1.20
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
NCT045647424,017 enrolled · 2020
Win Ratio (WR) 1.341.20 to 1.50
NCT030579773,730 enrolled · 2017
HR 0.750.65 to 0.86

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

5 citing papers in PubMed, 2 syntheses or guidelines pooled it.

  1. Pooled it
  2. Guideline
  3. Medical Management of Coronary Artery Disease: An Update.The International journal of angiology : official publication of the International College of Angiology, Inc · 2025
    Review
  4. Review
  5. Review
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

3 authors.

Yuxin Zhang *Center for Clinical and Epidemiologic Research, Beijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing Municipal Key Laboratory of Clinical Epidemiology, Beijing, China.
Zhaoji Li *Peking University Third Hospital, Beijing, China.
Yongchen HaoCenter for Clinical and Epidemiologic Research, Beijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing Municipal Key Laboratory of Clinical Epidemiology, Beijing, China. haoyongchen123@163.com.

Funding

Beijing Municipal Administration of Hospitals Incubating Program PX2023026
8 · The paper itself

Abstract

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

backgroundSodium-glucose transporters 2 inhibitors (SGLT-2i) and glucagon-like peptide 1 receptor agonists (GLP-1 RAs) are recommended along with metformin for the potential cardiovascular benefits among type 2 diabetes. This meta-analysis aims to evaluate whether the effects of SGLT-2i or GLP-1 RAs on cardiovascular outcomes are consistent with and without baseline metformin use.

methodsPubMed, Cochrane, Web of Science and Embase were searched for randomized placebo-controlled trials with SGLT-2i or GLP-1 RAs as interventions of type 2 diabetes patients up to June, 2024. The main outcomes were major adverse cardiovascular events (MACE), hospitalization for heart failure (HHF) or cardiovascular death. Both random-effects model and fixed model were adopted to estimate pooled hazard ratios (HR) and 95% confidence intervals (95% CI).

resultsA total of 81,738 patients (median age: 62-66 years, 53.7-71.5% men, median follow-up: 1.3-5.4 years) from 11 studies (7 studies of SGLT-2i and 4 of GLP-1 RAs) were included in the study. The metformin-naive portions ranged from 28.90% to 81.98%. Among patients using metformin at baseline, SGLT-2i or GLP-1 RAs reduced MACE risk (HR = 0.95, 95% CI 0.91-0.99, P = 0.02). In metformin-naive patients, similar reductions were observed (HR = 0.79, 95% CI 0.65-0.95, P = 0.01). No statistically significant interaction was found between metformin users and non-users for any outcome (all P values for interaction > 0.05), indicating consistent cardiovascular benefits regardless of baseline metformin therapy.

conclusionsSGLT-2i and GLP-1 RAs have the effects of cardiovascular benefits for T2DM patients regardless of baseline metformin use.

Indexed as

Cardiovascular DiseasesDiabetes Mellitus, Type 2Glucagon-Like Peptide-1 Receptor AgonistsMetforminRandomized Controlled Trials as TopicSodium-Glucose Transporter 2 InhibitorsHumansHypoglycemic AgentsMaleMiddle AgedGlucagon-Like Peptide-1 Receptor AgonistsHypoglycemic AgentsMetforminSodium-Glucose Transporter 2 InhibitorsCardiovascular diseaseGLP-1 RasMeta-analysisSGLT-2iType 2 diabetes

Identifiers

PMID39773332
PMCPMC11706166

What Socratic holds

Texttitle and abstract
LicenceCC BY-NC-ND
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.