CARDIOPROTECTIVE ACTIVITY OF EMPAGLIFLOZIN AND LIRAGLUTIDE IN DIABETIC RATS INDUCED WITH ACUTE MYOCARDIAL INFARCTION

• Main Author: Fathadina, Almira
• Format: Theses
• Language: Indonesia
• Online Access: https://digilib.itb.ac.id/gdl/view/66317
• Institution: Institut Teknologi Bandung

Type 2 diabetes mellitus (T2DM) is diabetes with the most prevalence over 90% of world diabetes, and significantly increases each year. If not well-controlled, DM will increase the risk of complication such as diabetic cardiomyopathy and myocardial infarction (MI) along with the increase of other cardiovascular risk factors. Cardiovascular benefit of new class anti-hyperglycaemic agent such as glucagon like peptide-1 receptor agonist (GLP-1RA) or sodium glucose cotransporter-2 inhibitor (SGLT2i) has been proven, with the proposed-mechanism that might be complementary. In this study, the effects of its combination were investigated against several parameters including diabetes and cardiac status on male Wistar rats. The rats were given Lipomed?20% MCT/LCT (20 ml/kg BW) by intragastric (i.g.) for 14 days to induce insulin resistance, then given streptozotocin (STZ) 35 mg/kg BW intraperitoneally (i.p.) to induce mild-tomoderate reduction of beta cell pancreas capacity that mimic pathology of T2DM. Diabetic state was confirmed by fasting blood glucose >150 mg/dL and KITT value that significantly different (p<0.05) from negative control. The rats were treated for 30 days as follows: negative control, DM, and DM+IM group were given CMC Na 0.5% i.g. and NaCl 0.9% subcutaneously (s.c.); liraglutide (0.062 mg/kg BW s.c.); empagliflozin (1 mg/kg BW i.g.); combination (liraglutide 0.062 mg/kg BW s.c. and empagliflozin 1 mg/kg BW i.g.). The rats received isoproterenol (ISO) 85 mg/kg BW on day 29 and 30 (at 24 hours interval). Blood samples were collected before and after MI induction for the estimation of cardiac biomarkers. The percentage inhibition (%) of combination group on creatine kinase (CK), CK- MB, aspartate transaminase (AST), alanine transaminase (ALT), and lactate dehydrogenase (LDH) biomarkers before MI were 71.36; 58.97; 64.45; 25.83; 47.53 respectively. While the percentage inhibition after MI were 70.51; 71.48; 73.05; 41.22; and 47.90 respectively. Higher inhibition with significant result p<0.05) in the combination group compared to empagliflozin/liraglutide alone were shown against CK-MB biomarkers in diabetic rats without MI, and against CK, CK-MB, LDH, and AST biomarkers on diabetic rats with MI.