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.
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.
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Who cites it
3 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Hepatoprotective effects of empagliflozin in metabolic dysfunction-associated steatotic liver disease: a systematic review and meta-analysis of preclinical studies.Frontiers in pharmacology · 2026Pooled it
- Empagliflozin in the Absence of Diabetes: A Systematic Review of Its Anthropometric and Metabolic Effects in Humans and Animals.International journal of endocrinology · 2026Article
- Research progress on the mechanistic pathways and biomarkers of therapeutic drugs for metabolic-associated steatotic liver disease.Frontiers in cell and developmental biology · 2026Review
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Authors and funding
13 authors.
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No grant is acknowledged in the PubMed record.
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.
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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 Socratic graph.