Comparison of the cardioprotective effects of liraglutide, dapagliflozin and their combination in a rat model of diabetes induced by streptozotocin

Abstract

Background: Sodium-glucose cotransporter 2 (SGLT2) inhibitors and glucagon-like peptide 1 (GLP-1) receptor agonists positively affect diabetic cardiac complications.

Aim: To evaluate and compare the impact of liraglutide, dapagliflozin, and their combination on cardiac biomarkers of inflammation, oxidative stress, and fibrosis in a rat model of streptozotocin (STZ)-induced diabetes.

Methods: Adult male Wistar rats were assigned into five groups (15-17 rats/group): control rats, diabetic rats (DM, single 50 mg/kg STZ intraperitoneally (IP)), diabetic rats treated with dapagliflozin (Dapa, 1 mg/kg by oral gavage), diabetic rats treated with liraglutide (Lira), 0.4 mg/kg subcutaneously (SC), and diabetic rats treated with both medications (Dapa+Lira) for 8 weeks. Cardiac biomarkers of inflammation, oxidative stress, and fibrosis were evaluated.

Results: Dapagliflozin and/or liraglutide treatment lowered glucose levels, mostly in the combination group. Diabetes increased heart/body weight ratio, which was normalized by all treatments. DM increased cardiac inflammatory and oxidant markers, including tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), endothelin-1 (ET-1), myeloperoxidase (1), plasminogen activator inhibitor-2 (PAI-2), total nitrite, and thiobarbituric acid reactive substances (TBARS). Dapagliflozin normalized inflammatory markers levels, but combination with Lira added no benefit, except for PAI-2. Dapagliflozin normalized total nitrite and TBARS levels. Combining treatments further decreased nitrite and TBARS levels and normalized cardiac SOD activity. Both dapagliflozin and the combination normalized cardiac fibrosis and platelet-derived growth factor-BB (PDGF-BB) levels.

Conclusion: Dapagliflozin reduced cardiac fibrosis, and attenuated oxidative stress, and inflammation more effectively than liraglutide. Combining treatments improved oxidative status. Our findings support using dapagliflozin to prevent cardiovascular diseases more than liraglutide.

Keywords: Cardiovascular disease; Dapagliflozin; Diabetes; Fibrosis; Glucagon-like peptide-1 receptor agonists; Inflammation; Liraglutide; Oxidative stress; Sodium-glucose cotransporter 2 inhibitors.