Evidence map›Paper›PMID 42396722›Full record

Trial reportDiabetes, obesity & metabolism2026

First-Line Dapagliflozin, Metformin, or Combination Therapy in Type 2 Diabetes: Vascular and Molecular Outcomes of a Randomised Controlled Trial.

Ying Jie Chee, Sanchalika Acharyya, Huiling Liew, Cherng Jye Seow, Liuh Ling Goh, Bernhard O Boehm, Rinkoo Dalan

Registry-linked trialAbstract readRandomized Controlled Trial
In one paragraph

Trial report in Diabetes, obesity & metabolism, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It reports registered trial NCT05440591. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · 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.

NCT05440591 phase4unknown status

Effects of Dapagliflozin and Metformin on Vascular Function in Newly-Diagnosed Treatment-Naive Type 2 Diabetes- A Randomised Controlled Trial (DMVascular Study)

Ran2019Enrolled150Registered outcomes5Posted comparisons0ConditionsDiabetesArmsdapagliflozin, Dapagliflozin / metFORMIN Pill, MetFORMIN 500 Mg Oral Tablet
Open the trial in the graph
3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Trial
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors.

Ying Jie CheeTan Tock Seng Hospital, National Healthcare Group, Singapore, Singapore.
Sanchalika AcharyyaTan Tock Seng Hospital, National Healthcare Group, Singapore, Singapore.
Huiling LiewTan Tock Seng Hospital, National Healthcare Group, Singapore, Singapore.
Cherng Jye SeowTan Tock Seng Hospital, National Healthcare Group, Singapore, Singapore.
Liuh Ling GohTan Tock Seng Hospital, National Healthcare Group, Singapore, Singapore.
Bernhard O BoehmKing's College London, London, UK.
Rinkoo DalanTan Tock Seng Hospital, National Healthcare Group, Singapore, Singapore.ORCID 0000-0001-9769-2696

Funding

National Medical Research Council MOH-000014
6 · The paper itself

Abstract

aimsThe optimal first-line pharmacological therapy for newly diagnosed type 2 diabetes mellitus (T2DM) remains uncertain. This trial compared the vascular and molecular effects of dapagliflozin monotherapy, metformin monotherapy, and their combination in this population. MATERIALS AND

methodsSixty participants were randomised 1:1:1 to metformin 500 mg twice daily (n = 19), dapagliflozin 10 mg once daily (n = 20), or dapagliflozin-metformin combination (n = 21) for 12 weeks. The primary endpoint was change in reactive hyperaemia index (RHI) from baseline. Secondary endpoints were pulse wave velocity (PWV) and carotid intima-media thickness (CIMT), analysed by ANCOVA. Exploratory sphingolipid and proteomics profiling was performed using partial least squares discriminant analysis and ROC curve analysis.

resultsRHI did not differ significantly between groups (primary endpoint). Dapagliflozin produced significantly greater CIMT reduction versus metformin as a secondary endpoint (-0.058 mm; 95% CI -0.106 to -0.010; p = 0.018). PWV changes were non-significant between groups. Sphingolipid profiling identified dapagliflozin-specific downregulation of pro-inflammatory lactosylceramide species, particularly LacCer(d18:0) (AUC 0.814). Proteomics revealed upregulation of EpCAM and downregulation of endothelial adhesion molecules (JAM-A, PECAM-1, vWF) and tissue plasminogen activator with dapagliflozin compared with metformin.

conclusionsIn treatment-naïve newly diagnosed T2DM, dapagliflozin produced significantly greater CIMT reduction versus metformin, accompanied by distinct sphingolipid and proteomic signatures suggesting pleiotropic cardioprotective mechanisms. These hypothesis-generating findings warrant validation in larger adequately powered trials.

trial registrationClinicalTrials.gov identifier: NCT05440591.

Indexed as

Benzhydryl CompoundsDiabetes Mellitus, Type 2Diabetic AngiopathiesGlucosidesHypoglycemic AgentsMetforminAgedCarotid Intima-Media ThicknessDrug Therapy, CombinationFemaleHumansMaleMiddle AgedProteomicsPulse Wave AnalysisSphingolipidsBenzhydryl CompoundsdapagliflozinGlucosidesHypoglycemic AgentsMetforminSphingolipidscarotid intima‐media thicknessmetforminproteomicssodium‐glucose transporter 2 inhibitors (covers dapagliflozin)sphingolipidstype 2 diabetes mellitus

Identifiers

PMID42396722
PMCPMC13449050

What OpenQuestion holds

Texttitle and abstract
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Registered trials

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.