Triple verses glimepiride plus metformin therapy on cardiovascular risk biomarkers and diabetic cardiomyopathy in insulin resistance type 2 diabetes mellitus rats

IRtype2DM patients are often treated with a combination of antidiabetic agents. Drugs with different complementary mechanisms of action frequently used in daily clinical practice but glycemic control with monotherapeutic attempts fail in the long run. To date, biomarkers for cardiovascular risk and insulin sensitivity with combination of triple oral hypoglycemic therapies are not fully revelled in view of additional cardiovascular risk reduction. In the present study, IRtype2DM induced by administering streptozotocin (90 mg/kg, i.p.) in neonatal rat model. IRtype2DM rats were selected by determining FPI [>60 pmol/l]; HOMA-IR & Hyperinsulinemic euglycemic clamp technique at 6 weeks and then treated for 8 weeks with (i) Metformin (120 mg/kg, o.d.) + Glimepiride (1 mg/kg, o.d.), (ii) Metformin (265 mg/kg, o.d.) + Rosiglitazone (1 mg/kg, o.d.) + Glimepiride (0.7 mg/kg, o.d.). At the end cardiovascular risk parameters evaluated by ELISA kits and insulin sensitivity were determined by HOMA-IR. In conclusion, triple oral hypoglycemic therapy improves glycemic control, insulin sensitivity, retards diabetic cardiomyopathy and does not increased body weight; decrease more detrimental inflammatory markers, increase interlukin-10 and adiponectin in neonatal streptozotocin-induced IRtype2DM Wistar Albino Rats. Triple therapy showed a synergistic effect and was promising in insulin resistance, better in additional cardiovascular risk reduction and those nonresponders to metformin add on glimepiride therapy.