Liraglutide and Empagliflozin Alleviate Diabetic Cardiomyopathy by Reducing Oxidative Stress and Inflammation

Abstract

Background: Diabetes mellitus (DM) is a growing metabolic disease worldwide, associated with severe complications. Glucagon-like peptide-1 analogs and sodium-glucose cotransporter-2 inhibitors are promising therapeutic options for diabetic cardiomyopathy (DCM), although their cardioprotective mechanisms are not yet fully understood. Objective: This study evaluates the effects of liraglutide and empagliflozin on oxidative stress, inflammation, and histological changes in cardiac tissue in DCM. Materials and methods: Thirty-seven male Wistar albino rats were divided into four groups. Diabetes was induced in three groups using streptozotocin and nicotinamide. The groups were: (1) Control, (2) DM, (3) DM + Liraglutide (0.6 mg/kg, subcutaneously, 8 weeks), and (4) DM + Empagliflozin (30 mg/kg, oral gavage, 8 weeks). Blood samples were analyzed through enzyme-linked immunosorbent assay for tumor necrosis factor-α (TNF-α), interleukin-1 (IL-1), malondialdehyde (MDA), superoxide dismutase (SOD), advanced glycation end (AGE) products, and insulin. Cardiac tissue was examined histopathologically. Results: Diabetes significantly increased blood glucose, IL-1, TNF-a, MDA, and AGE (p < 0.01), while SOD levels decreased (p < 0.01), alongside myocardial damage. Liraglutide and empagliflozin improved all parameters (p < 0.01). Conclusion: Liraglutide and empagliflozin mitigate diabetes-induced cardiac damage, likely by reducing fibrosis, oxidative stress, and inflammation. © 2025 Academia Nacional de Medicina de México, A.C. Publicado por Permanyer.