Effects of SGLT2 Inhibitors and GLP-1 Receptor Agonists on Renin-Angiotensin-Aldosterone System

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

Search for a Higgs boson decaying into γ∗γ→llγ\gamma^* \gamma \to ll \gamma with low dilepton mass in pp collisions at s=8\sqrt{s} = 8 TeV

A search is described for a Higgs boson decaying into two photons, one of which has an internal conversion to a muon or an electron pair (ll gamma). The analysis is performed using proton-proton collision data recorded with the CMS detector at the LHC at a centre-of-mass energy of 8 TeV, corresponding to an integrated luminosity of 19.7 inverse femtobarns. The events selected have an opposite-sign muon or electron pair and a high transverse momentum photon. No excess above background has been found in the three-body invariant mass range 120<m[ll gamma]<150 GeV, and limits have been derived for the Higgs boson production cross section times branching fraction for the decay H to gamma* gamma to ll gamma, where the dilepton invariant mass is less than 20 GeV. For a Higgs boson with m[H]=125 GeV, a 95% confidence level (CL) exclusion observed (expected) limit is 7.7 (6.4+3.1/-2.0) times the standard model prediction. Additionally, an upper limit at 95% CL on the branching fraction of H to(JPsi) gamma for the 125 GeV Higgs boson is set at 1.5E-3