Evidence map›Paper›PMID 41680826›Full record

Trial reportCardiovascular diabetology2026

Timing-dependent anti-inflammatory effects of empagliflozin in monocyte-derived macrophages from post-myocardial infarct patients with type 2 diabetes.

Chelsy L Cliff, Muhammad U Shah, Joanna K Ward, Maxime Inghels, Kelvin Lee, Paul E Squires, Claire E Hills

Abstract readRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Cardiovascular diabetology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

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

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

5 citing papers in PubMed.

  1. Article
  2. Review
  3. Review
  4. Article
  5. Review
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.

Chelsy L Cliff *College of Health and Science, University of Lincoln, Lincoln, LN6 7DL, UK.
Muhammad U Shah *College of Health and Science, University of Lincoln, Lincoln, LN6 7DL, UK.
Joanna K WardCollege of Health and Science, University of Lincoln, Lincoln, LN6 7DL, UK.
Maxime InghelsCollege of Health and Science, University of Lincoln, Lincoln, LN6 7DL, UK.
Kelvin LeeCollege of Health and Science, University of Lincoln, Lincoln, LN6 7DL, UK.
Paul E SquiresCollege of Health and Science, University of Lincoln, Lincoln, LN6 7DL, UK.
Claire E HillsCollege of Health and Science, University of Lincoln, Lincoln, LN6 7DL, UK. chills@lincoln.ac.uk.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

BACKGROUND AND

objectiveInflammation drives early recurrent cardiovascular risk in type 2 diabetes mellitus (T2DM) patients following acute myocardial infarction (AMI), particularly within 30-90 days post-discharge. Sodium-glucose co-transporter 2 (SGLT2) inhibitors such as empagliflozin (EMPA) provide cardiometabolic benefits, but their anti-inflammatory effects and optimal timing after AMI remain unclear. Given the prognostic role of systemic markers like the neutrophil-to-lymphocyte ratio, we investigated whether early initiation of EMPA modulates NOD-like receptor protein-3 (NLRP3) inflammasome activity and inflammatory responses in monocyte-derived macrophages (MDMs) from T2DM-AMI patients.

methodsSixty-six participants were randomised to receive EMPA either at discharge (Arm-A) or following a 90-day delay (Arm B). Clinical data and biological samples were collected over 180 days. CD14+ MDMs and plasma were obtained at days 0, 30, and 90 (EMPA vs. no EMPA), and days 90, 120, and 180 (early vs. delayed). Inflammatory and metabolic markers were assessed using RT-qPCR, luminescence-based caspase-1 and ATP assays, and targeted immunoassays.

resultsEarly EMPA administration was associated with reduced NLRP3 priming (IL1β mRNA) and activation (caspase-1 activity), potentially linked to decreased release of ATP, a danger associated molecular pattern (DAMP). In the absence of EMPA, pro-inflammatory cytokines (TNFα, IL6, MCP1) and M1 macrophage markers (e.g., CD80) either increased or remained unchanged over time. Early EMPA treatment appeared to stabilise or reduce their expression. Markers of cell senescence (p21, IL8, BCL2) were also modulated. Plasma levels of senescence-associated markers (MMP9, OPN, Serpin E1) remained largely unchanged, highlighting the importance of evaluating macrophage-specific responses.

conclusionEarly empagliflozin administration in T2DM-AMI patients was associated with modulation of NLRP3-related inflammatory and senescence pathways in patient-derived macrophages, benefits observed when cells were stimulated ex-vivo with an inflammatory stimulus. These findings provide mechanistic insight into the timing-dependent anti-inflammatory effects of EMPA and underscore its potential for immediate post-AMI use to reduce inflammation and lower residual cardiovascular risk, supporting further clinical investigation.

Indexed as

Anti-Inflammatory AgentsBenzhydryl CompoundsDiabetes Mellitus, Type 2Inflammation MediatorsMacrophagesMyocardial InfarctionSodium-Glucose Transporter 2 InhibitorsAgedCells, CulturedDrug Administration ScheduleFemaleGlucosidesHumansInflammasomesMaleMiddle AgedAnti-Inflammatory AgentsBenzhydryl CompoundsempagliflozinGlucosidesInflammasomesInflammation MediatorsNLR Family, Pyrin Domain-Containing 3 ProteinNLRP3 protein, humanSodium-Glucose Transporter 2 Inhibitors

Identifiers

PMID41680826
PMCPMC12896262

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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.