Non Incretin Effects of DPP-4 Inhibitors: Comparative Study

Abstract

Background: Diabetes mellitus is a metabolic syndrome that adversely affects all parts of the body especially the cardiovascular system. Dipeptidyl peptidase-4 (DPP-4) is a multifunctional protein and its inhibition has diverse effects. DPP-4 inhibition was shown to improve the survival rate after myocardial infarction in mice. Beneficial myocardial metabolic effects of DPP-4 inhibitors have been observed in experimental models. Cardiovascular outcome trials of DPP-4 inhibitors show variable adverse cardiovascular events. Objective: This experimental study was aimed to study the direct cardiovascular effects of DPP-4 Inhibitors on chronotropicity (Heart Rate, HR), inotropicity (Apical Force and; dP/dt(max), ECG and Coronary Flow(C.F) and detect its potential useful and harmful effects on cardiovascular parameters. Methods: The effects of graded doses (10-9 - 10-6M) of Sitagliptin (S) and Vildagliptin(V) were observed on retrograde perfused isolated rabbit hearts with warm Krebs-Henseliet solution on Radnoti working heart system. Fifty four(54) rabbits were grouped into nine groups i.e ; I(S1), II(S2), III(S3), IV(S4), V(S5), VI(S6), VII(V1), and VIII(V2) and IX(V3) each comprising of six animals(n=6).Effects of experimental drugs were observed on chronotropicity(HR), inotropicity (Apical Force and Peak rate of rise of LVP i.e; dP/dt(max) and Coronary flow(CF). The results were statistically analyzed with Graph Pad Grism and wherever necessary paired or unpaired “t” test was applied. Conclusion: Sitagliptin and Vildagliptin both have suppressant effects on HR. Sitagliptin has positive and Vildagliptin had negative inotropic effects. Both drugs (10-8 - 10-6M); decrease coronary flow but have no significant effect on ECG.