ANGIOTENSIN PROFILES IN PATIENTS WITH HYPERTENSION AND TYPE 2 DIABETES WITH COMBINATION THERAPY OF EMPAGLIFLOZIN AND LINAGLIPTIN VERSUS METFORMIN AND INSULIN GLARGINE

Abstract

Objective: The renin-angiotensin system (RAS) plays a key role in the physiological regulation of blood pressure. Patients with type-2-diabetes-mellitus (T2DM) and hypertension are known to have increased RAS activity. However, the precise role of RAS activation after SGLT2-inhibitor therapy is unknown. The classic RAS comprises the ACE-AngII-AT1R-axis (classic-axis) that promotes vasoconstriction. The Angiotensin-converting-enzyme-2-angiotensin-(1–7)-Mas axis (Mas-axis) with its components Angiotensin-(1–7) (Ang-1–7) and Angiotensin-(1–5) (Ang-1–5) is an endogenous negative regulatory pathway of the classic-axis, which can reduce its harmful effects. Design and method: Angiotensin profiles were determined in 55 patients with hypertension and T2DM from our double blind, randomized, placebo controlled clinical trial “Effects of Empagliflozin+Linagliptin (E+L) vs Metformin+Insulin Glargine (M+I) on Renal and Vascular Changes in Type 2 Diabetes’’ (ELMI) at baseline and three months after application of either E+L or M+I. An LC-MS/MS based approach was used to simultaneously quantify individual angiotensin metabolites (Attoquant Diagnostics, Vienna, Austria). Results: In the E+L group medication induced a rise in Ang-I, Ang-(1–7) and a trend to a rise in Ang-II between baseline and treatment, which was not present in the M+I group (table). Comparison between the E+L and M+I group revealed that change between baseline and treatment was significantly different for Ang I (p = 0.002) and Ang-(1–7) (p = 0.002) between the groups. No difference in change between baseline and treatment was found for Ang II (p = 0.182) and Ang-(1–5) (p = 0.224) between the E+L and M+I group. Conclusions: In patients with hypertension and T2DM three months of therapy with E+L led to a rise of classic and protective components of the RAS, which was not present in the M+I group. The biological consequence of this complex RAS activation remains to be elucidated.