SGLT2 inhibitor dapagliflozin prevents atherosclerotic and cardiac complications in experimental type 1 diabetes

• Published in: PloS one Vol. 17; no. 2; p. e0263285
• Main Authors: Hodrea, Judit, Saeed, Adar, Molnar, Agnes, Fintha, Attila, Barczi, Adrienn, Wagner, Laszlo J, Szabo, Attila J, Fekete, Andrea, Balogh, Dora B
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 17-02-2022; Public Library of Science (PLoS)
• Subjects: Animals; Antidiabetics; Aorta; Arteriosclerosis; Atherosclerosis; Atherosclerosis - etiology; Atherosclerosis - metabolism; Atherosclerosis - pathology; Atherosclerosis - prevention & control; Benzhydryl Compounds - pharmacology; Biology and Life Sciences; Blood Glucose - analysis; Blood pressure; Cardiovascular diseases; Care and treatment; Clinical trials; Complications; Complications and side effects; Congestive heart failure; Coronary vessels; Cytokines; Dapagliflozin; Diabetes; Diabetes mellitus; Diabetes mellitus (insulin dependent); Diabetes Mellitus, Experimental - complications; Diabetes Mellitus, Experimental - drug therapy; Diabetes Mellitus, Type 1 - complications; Diabetes Mellitus, Type 1 - drug therapy; FDA approval; Fibrosis; Glucose; Glucosides - pharmacology; Heart diseases; Heart failure; Heart Failure - etiology; Heart Failure - metabolism; Heart Failure - pathology; Heart Failure - prevention & control; Hypertrophy; Inflammation; Laboratory animals; Male; Medical research; Medicine and Health Sciences; Metabolism; Molecular modelling; Mortality; Patient outcomes; Pediatrics; Prevention; Rats; Rats, Wistar; Risk factors; Sodium; Sodium-glucose cotransporter; Sodium-Glucose Transporter 2 Inhibitors - pharmacology; Streptozocin; Thickening; Type 1 diabetes; Urine; Hungary; United States > US; Germany
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0263285

Cardiovascular disease (CVD) is two to five times more prevalent in diabetic patients and is the leading cause of death. Therefore, identification of novel therapeutic strategies that reduce the risk of CVD is a research priority. Clinical trials showed that reduction in the relative risk of heart failure by sodium-glucose cotransporter 2 inhibitors (SGLT2i) are partly beyond their glucose lowering effects, however, the molecular mechanisms are still elusive. Here we investigated the role of SGLT2i dapagliflozin (DAPA) in the prevention of diabetes-induced cardiovascular complications.
Type 1 diabetes was induced with streptozotocin (65 mg/bwkg, ip.) in adult, male Wistar rats. Following the onset of diabetes rats were treated for six weeks with DAPA (1 mg/bwkg/day, po.).
DAPA decreased blood glucose levels (D: 37±2.7 vs. D+DAPA: 18±5.6 mmol/L; p<0.05) and prevented metabolic decline. Aortic intima-media thickening was mitigated by DAPA. DAPA abolished cardiac hypertrophy, and myocardial damage. Cardiac inflammation and fibrosis were also moderated after DAPA treatment.
These data support the preventive and protective role of SGLT2i in diabetes-associated cardiovascular disease. SGLT2i may provide novel therapeutic strategy to hinder the development of cardiovascular diseases in type 1 diabetes, thereby improve the outcomes.