Therapeutic effects of finerenone and exenatide on diabetes-induced heart failure: A combined approach targeting inflammation and oxidative stress.

Cardiovascular complications, particularly diabetic cardiomyopathy and heart failure, are leading causes of morbidity and mortality in patients with diabetes mellitus. This study aimed to investigate the therapeutic potential of finerenone and exenatide, individually and in combination, in mitigating diabetes-induced cardiac injury. Finerenone, a non-steroidal mineralocorticoid receptor antagonist, exhibits strong anti-fibrotic and anti-inflammatory properties in cardiovascular and renal diseases. Exenatide, a glucagon-like peptide-1 receptor agonist, is recognized for its glucose-lowering effects and additional cardioprotective actions, including antioxidant and anti-inflammatory activities. The combination of these agents was hypothesized to exert synergistic effects by targeting complementary pathological pathways involved in diabetic cardiomyopathy progression. Type 1 diabetes was induced in rats by a single high-dose streptozotocin injection. Animals were divided into five groups: control, STZ, STZ with finerenone, STZ with exenatide, and STZ with both finerenone and exenatide. Cardiac tissues and serum samples were analyzed for oxidative stress markers (TOS, TAS), inflammatory cytokines (IL-6, IL-1β, TNF-α), and myocardial injury biomarkers (cTnT, cTnI) through RT-qPCR and Western blotting. NRF2 pathway activation was also evaluated to assess antioxidant responses. STZ-induced diabetic rats showed significant increases in hyperglycemia, inflammation, oxidative stress, and myocardial injury. Treatment with either finerenone or exenatide alone improved several parameters; however, the combination therapy provided the most substantial cardioprotective effects, with marked reductions in oxidative stress and inflammation and enhanced NRF2 expression. These findings suggest that the combined administration of finerenone and exenatide offers superior protection against diabetes-induced cardiac injury compared to monotherapies, supporting a dual-targeted therapeutic approach for diabetic cardiomyopathy.