Author:
Puglisi Soraya,Rossini Alessandro,Poli Roberta,Dughera Francesca,Pia Anna,Terzolo Massimo,Reimondo Giuseppe
Abstract
Sodium-glucose cotransporters inhibitors (SGLT2-i) and GLP-1 receptor agonists (GLP1-RA) are glucose-lowering drugs that are proved to reduce the cardiovascular (CV) risk in type 2 diabetes mellitus (T2DM). In this process, the renin-angiotensin-aldosterone system (RAAS) is assumed to play a role. The inhibition of SGLT2 improves hyperglycemia hampering urinary reabsorption of glucose and inducing glycosuria. This “hybrid” diuretic effect, which couples natriuresis with osmotic diuresis, potentially leads to systemic RAAS activation. However, the association between SGLT2-i and systemic RAAS activation is not straightforward. Available data indicate that SGLT2-i cause plasma renin activity (PRA) increase in the early phase of treatment, while PRA and aldosterone levels remain unchanged in chronic treated patients. Furthermore, emerging studies provide evidence that SGLT2-i might have an interfering effect on aldosterone/renin ratio (ARR) in patients with T2DM, due to their diuretic and sympathoinhibition effects. The cardio- and reno-protective effects of GLP-1-RA are at least in part related to the interaction with RAAS. In particular, GLP1-RA counteract the action of angiotensin II (ANG II) inhibiting its synthesis, increasing the inactivation of its circulating form and contrasting its action on target tissue like glomerular endothelial cells and cardiomyocytes. Furthermore, GLP1-RA stimulate natriuresis inhibiting Na+/H+ exchanger NHE-3, which is conversely activated by ANG II. Moreover, GLP1 infusion acutely reduces circulating aldosterone, but this effect does not seem to be chronically maintained in patients treated with GLP1-RA. In conclusion, both SGLT2-i and GLP1-RA seem to have several effects on RAAS, though additional studies are needed to clarify this relationship.
Funder
Università degli Studi di Torino
Subject
Endocrinology, Diabetes and Metabolism
Reference94 articles.
1. Economic Costs of Diabetes in the U.S. @ in 2017;Diabetes Care,2018
2. Impact of Cardiovascular Complications Among Patients With Type 2 Diabetes Mellitus: A Systematic Review;Vaidya;Expert Rev Pharmacoecon Outcomes Res,2015
3. Global Burden of Diabetes, 1995-2025: Prevalence, Numerical Estimates, and Projections;King;Diabetes Care,1998
4. IDF Diabetes Atlas: Global Estimates of the Prevalence of Diabetes for 2011 and 2030;Whiting;Diabetes Res Clin Pract,2011
5. ESC Guidelines on Diabetes, Pre-Diabetes, and Cardiovascular Diseases Developed in Collaboration With the EASD;Cosentino;Eur Heart J,2020
Cited by
35 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献