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Abstract Background: Cardiac affection is common in diabetic patients. Although insulin exerts a cardioprotective role, it may not be enough to totally prevent this affection. Sitagliptin or metformin combined with insulin not only help controlling the bloodglucose, but they also have a direct cardioprotective effect. Methods:An experimental study was done on 60 male albino rats for a duration of 42 days. Diabetes mellitus (DM) was induced bya single intraperitoneal injection of streptozotocin (60 mg). After confirming DM, rats were treated witheither insulin alone in two different doses (3 and 6 IU) or insulin (3 IU) and metformin (300 mg/Kg/day) or sitagliptin (10 mg/Kg) (n=10). Echocardiography was done at days 14, 28 and at the end of experimental procedures.Blood samples were collected for estimation of serum levels of random blood glucose, tumor necrosis factor alpha, interleukin-6 and brain natriuretic peptide. Results:DM significantly affected the cardiac condition very early as evidenced by deterioration of ejection fraction and other echocardiographic and laboratory parameters compared to non-diabetic rats. Treatment of DM with insulin and control of blood glucose prevented the deterioration of the cardiac condition.The addition of either metformin or sitagliptin significantly potentiate the cardioprotective effects of insulin |