ArticleDiabetology & metabolic syndrome2023
Therapeutic effects on the development of heart failure with preserved ejection fraction by the sodium-glucose cotransporter 2 inhibitor dapagliflozin in type 2 diabetes.
Article in Diabetology & metabolic syndrome, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed.
- Mechanistic insights into the mitigating role of dapagliflozin against radiation-triggered myocardial apoptosis: gating to AMPK-regulated autophagic machinery.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Mechanisms and Therapeutic Potential of Sodium-Glucose Cotransporter 2 Inhibitors in Heart Failure.Reviews in cardiovascular medicine · 2026Review
- Integrated Multi-Omics Analysis Identifies PDK4 and ACOT1 as Metabolic Hub Genes Associated With Myocardial Fibrosis in Diabetic Cardiomyopathy.Journal of diabetes research · 2026Article
- Pathogenesis and Therapeutic Advances in Heart Failure with Preserved Ejection Fraction.Reviews in cardiovascular medicine · 2026Review
- Review
- Early cardioprotective effects of SGLT2i on hypertensive cardiac remodeling via STIM1/Orai1-dependent calcium signaling: beyond blood pressure control.Journal of bioenergetics and biomembranes · 2025Article
- Multi-omics analysis of diabetic cardiomyopathy pathogenesis using a type 2 diabetic Zucker diabetic fatty rat model.Scientific reports · 2025Article
- The landscape of novel antidiabetic drugs in diabetic HFpEF: relevant mechanisms and clinical implications.Cardiovascular diabetology · 2025Review
- Cardioprotective Effects of Dapagliflozin and Trimetazidine on Doxorubicin-Induced Cardiotoxicity in Streptozotocin-Induced Type 1 Diabetic Rats via Endoplasmic Reticulum Stress.Journal of clinical medicine · 2025Article
- Metabolomics Insights into the Benefits of SGLT2 Inhibitors in Type 2 Diabetes.Clinical pharmacology : advances and applications · 2025Review
- Mitochondrial dysfunction as a therapeutic nexus in HFpEF: therapeutic target and pharmacological advances.Frontiers in pharmacology · 2025Review
- Repurposing Dapagliflozin for Mitigation of the Kidney Injury Triggered by Cadmium in Rats: Role of Autophagy, Apoptosis, and the SIRT1/Nrf2/HO-1 Pathway.Pharmaceuticals (Basel, Switzerland) · 2024Article
- [Diabetic cardiomyopathy: a focus on sodium-glucose cotransporter type 2 inhibitors].Revista medica del Instituto Mexicano del Seguro Social · 2024Review
- mTORC1 and SGLT2 Inhibitors-A Therapeutic Perspective for Diabetic Cardiomyopathy.International journal of molecular sciences · 2023Review
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9 authors.
Funding
Abstract
backgroundHeart failure with preserved ejection fraction (HFpEF) is a common disease with high morbidity and lacks effective treatment. We investigated the protective effects of the long-term application of the sodium-glucose cotransporter 2 inhibitor (SGLT2i) dapagliflozin on diabetes-associated HFpEF in a rat model. Serum proteomics and metabolomics analysis were also conducted in type 2 diabetic patients with HFpEF treated with dapagliflozin.
methodsMale Zucker diabetic fatty (ZDF) rats were used as a model of diabetic cardiomyopathy. From weeks 16 to 28, animals were given a vehicle or dapagliflozin (1 mg/kg) once daily. Primary blood biochemistry indices, echocardiography, histopathology, and cardiac hemodynamics were determined during the study period. The key markers of myocardial fibrosis, nitro-oxidative stress, inflammation, apoptosis, autophagy, and AMPK/mTOR signaling were examined. Additionally, healthy controls and individuals with type 2 diabetes were enrolled and 16 serum samples from 4 groups were randomly selected. Serum proteome and metabolome changes after dapagliflozin treatment were analyzed in diabetic individuals with HFpEF.
resultsDapagliflozin effectively prevented the development of HFpEF in rats with diabetes by mitigating nitro-oxidative stress, pro-inflammatory cytokines, myocardial hypertrophy, and fibrosis, reducing apoptosis, and restoring autophagy through AMPK activating and mTOR pathway repressing. Proteomics and metabolomics revealed that cholesterol and high-density lipoprotein particle metabolism, nicotinate and nicotinamide metabolism, arginine biosynthesis, and cAMP and peroxisome proliferator-activated receptor (PPAR) signaling are the major disturbed pathways in HFpEF patients treated with dapagliflozin.
conclusionLong-term treatment with dapagliflozin significantly prevented the development of HFpEF in diabetic rats. Dapagliflozin could be a promising therapeutic strategy in managing HFpEF individuals with type 2 diabetes.
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