Evidence mapPaperPMID 41009577Full record

ArticleInternational journal of molecular sciences2025

The Combination Empagliflozin/Metformin Attenuates the Progression of Metabolic Dysfunction-Associated Steatotic Liver Disease in a Diet-Induced Experimental Rat Model.

Oscar René Zambrano-Vásquez, Fernando Cortes-Camacho, Juan Carlos Cabrera-Angeles, Ana Lilia Hernández-Alba, Fernando Enrique García-Arroyo, Jorge Ismael Castañeda-Sánchez, Elena Aréchaga-Ocampo, Omar Emiliano Aparicio-Trejo, Leonardo Del Valle-Mondragón, Constanza Estefanía Martínez-Olivares and 3 more

Abstract read
In one paragraph

Article in International journal of molecular sciences, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed, 1 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.

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

3 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Article
  3. 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

13 authors.

Oscar René Zambrano-VásquezDoctorado en Ciencias Biológicas y de la Salud, Universidad Autónoma Metropolitana, Mexico City 14387, Mexico.ORCID 0009-0005-6645-9054
Fernando Cortes-CamachoDoctorado en Ciencias Biológicas y de la Salud, Universidad Autónoma Metropolitana, Mexico City 14387, Mexico.
Juan Carlos Cabrera-AngelesSección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina, Instituto Politécnico Nacional, Mexico City 11340, Mexico.ORCID 0009-0001-0649-9338
Ana Lilia Hernández-AlbaSección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina, Instituto Politécnico Nacional, Mexico City 11340, Mexico.ORCID 0009-0002-5856-1137
Fernando Enrique García-ArroyoDepartamento de Fisiopatología Cardio-Renal, Instituto Nacional de Cardiología Ignacio Chávez, Mexico City 14080, Mexico.
Jorge Ismael Castañeda-SánchezDepartment of Biological Systems, Universidad Autónoma Metropolitana-Xochimilco, Mexico City 04960, Mexico.ORCID 0000-0002-4323-4988
Elena Aréchaga-OcampoDepartment of Natural Sciences, Universidad Autónoma Metropolitana-Cuajimalpa, Mexico City 05348, Mexico.ORCID 0000-0002-0787-5593
Omar Emiliano Aparicio-TrejoDepartamento de Fisiopatología Cardio-Renal, Instituto Nacional de Cardiología Ignacio Chávez, Mexico City 14080, Mexico.
Leonardo Del Valle-MondragónDepartamento de Farmacología, Instituto Nacional de Cardiología Ignacio Chávez, Mexico City 14080, Mexico.
Constanza Estefanía Martínez-OlivaresExperimental Pathology Department, Instituto Nacional de Ciencia Médicas y Nutrición "Salvador Zubirán", Mexico City 14080, Mexico.ORCID 0000-0001-5128-7695
Rogelio Hernández-PandoExperimental Pathology Department, Instituto Nacional de Ciencia Médicas y Nutrición "Salvador Zubirán", Mexico City 14080, Mexico.ORCID 0000-0003-1292-3833
Laura Gabriela Sánchez-LozadaDepartamento de Fisiopatología Cardio-Renal, Instituto Nacional de Cardiología Ignacio Chávez, Mexico City 14080, Mexico.
Horacio Osorio-AlonsoDepartamento de Fisiopatología Cardio-Renal, Instituto Nacional de Cardiología Ignacio Chávez, Mexico City 14080, Mexico.ORCID 0000-0002-9238-4202

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Metabolic dysfunction-associated steatotic liver disease (MASLD) encompasses several cardiometabolic risk factors (obesity, insulin resistance, diabetes, and dyslipidemia), in addition to hepatic steatosis. Therefore, treatment is often challenging and frequently involves polypharmacy. This study investigated whether the combination of empagliflozin/metformin improves MASLD disease outcomes in an experimental model of metabolic syndrome (MS). To evaluate the efficacy of the empagliflozin/metformin (12.5/850 mg/kg/day/30 days) combination, male Wistar rats (200-220 g) were fed a Western-type diet and sugary drink to induce MS. Biochemical parameters, markers of liver damage, oxidative stress, and histopathological analysis were assessed. Also, the expression of transcription factors associated with carbohydrate and lipid metabolism and the modulation of oxidative stress were assessed. The analyses were performed with the combination and with the drugs independently. The combination empagliflozin/metformin decreased body weight, plasma triglycerides, and total cholesterol levels, while improving fasting blood glucose, oral glucose tolerance test, and plasma HDL-cholesterol levels. Additionally, it prevented hepatic hypertrophy, liver damage at both biochemical and histological levels, and intrahepatic lipid accumulation. The combination also demonstrated a significantly greater effect in improving mitochondrial function and reducing oxidative stress by modulating the Nrf2-mediated pathway. The empagliflozin/metformin combination therapy mitigates MASLD progression, likely by improving liver and mitochondrial function, and attenuating oxidative stress. Notably, co-therapy shows greater beneficial effects than single treatments. This protective effect appears to involve modulation of key transcription factors regulating lipid and carbohydrate metabolism, as well as influencing endogenous antioxidant defenses.

Indexed as

Benzhydryl CompoundsFatty LiverGlucosidesMetabolic SyndromeMetforminAnimalsDiet, WesternDisease Models, AnimalDisease ProgressionDrug Therapy, CombinationLipid MetabolismLiverMaleOxidative StressRatsRats, WistarBenzhydryl CompoundsempagliflozinGlucosidesMetformindyslipidemiaempagliflozinlipid accumulationmetabolic dysfunction-associated steatotic liver diseasemetabolic syndromemetforminoxidative stress

Identifiers

PMID41009577
PMCPMC12470015

What Socratic holds

Texttitle and abstract
LicenceCC BY
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.