PMID- 34745006
OWN - NLM
STAT- MEDLINE
DCOM- 20220214
LR  - 20220214
IS  - 1664-2392 (Print)
IS  - 1664-2392 (Electronic)
IS  - 1664-2392 (Linking)
VI  - 12
DP  - 2021
TI  - Effects of SGLT2 Inhibitors and GLP-1 Receptor Agonists on 
      Renin-Angiotensin-Aldosterone System.
PG  - 738848
LID - 10.3389/fendo.2021.738848 [doi]
LID - 738848
AB  - 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.
CI  - Copyright (c) 2021 Puglisi, Rossini, Poli, Dughera, Pia, Terzolo and Reimondo.
FAU - Puglisi, Soraya
AU  - Puglisi S
AD  - Internal Medicine, Department of Clinical and Biological Sciences, San Luigi 
      Gonzaga Hospital, University of Turin, Orbassano, Italy.
FAU - Rossini, Alessandro
AU  - Rossini A
AD  - Endocrinology and Diabetes Unit, ASST Papa Giovanni XXIII, Bergamo, Italy.
FAU - Poli, Roberta
AU  - Poli R
AD  - Metabolic Disease and Diabetes Unit, San Luigi Gonzaga Hospital, Orbassano, 
      Italy.
FAU - Dughera, Francesca
AU  - Dughera F
AD  - Internal Medicine, Department of Clinical and Biological Sciences, San Luigi 
      Gonzaga Hospital, University of Turin, Orbassano, Italy.
FAU - Pia, Anna
AU  - Pia A
AD  - Internal Medicine, Department of Clinical and Biological Sciences, San Luigi 
      Gonzaga Hospital, University of Turin, Orbassano, Italy.
FAU - Terzolo, Massimo
AU  - Terzolo M
AD  - Internal Medicine, Department of Clinical and Biological Sciences, San Luigi 
      Gonzaga Hospital, University of Turin, Orbassano, Italy.
FAU - Reimondo, Giuseppe
AU  - Reimondo G
AD  - Internal Medicine, Department of Clinical and Biological Sciences, San Luigi 
      Gonzaga Hospital, University of Turin, Orbassano, Italy.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
DEP - 20211021
PL  - Switzerland
TA  - Front Endocrinol (Lausanne)
JT  - Frontiers in endocrinology
JID - 101555782
RN  - 0 (Blood Glucose)
RN  - 0 (Glucagon-Like Peptide-1 Receptor)
RN  - 0 (Sodium-Glucose Transporter 2 Inhibitors)
RN  - 4964P6T9RB (Aldosterone)
RN  - EC 3.4.23.15 (Renin)
SB  - IM
MH  - Aldosterone/blood
MH  - Blood Glucose
MH  - Glucagon-Like Peptide-1 Receptor/*agonists
MH  - Humans
MH  - Renin/blood
MH  - Renin-Angiotensin System/*drug effects
MH  - Sodium-Glucose Transporter 2 Inhibitors/*pharmacology
PMC - PMC8567993
OTO - NOTNLM
OT  - aldosterone
OT  - cardiovascular disease
OT  - cardiovascular risk
OT  - diabetes mellitus type 2
OT  - diabetic kidney disease
OT  - glucagon-like peptide-1 receptor agonist
OT  - renin
OT  - sodium-glucose cotransporter-2 inhibitor
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2021/11/09 06:00
MHDA- 2022/02/15 06:00
PMCR- 2021/01/01
CRDT- 2021/11/08 06:35
PHST- 2021/07/09 00:00 [received]
PHST- 2021/09/30 00:00 [accepted]
PHST- 2021/11/08 06:35 [entrez]
PHST- 2021/11/09 06:00 [pubmed]
PHST- 2022/02/15 06:00 [medline]
PHST- 2021/01/01 00:00 [pmc-release]
AID - 10.3389/fendo.2021.738848 [doi]
PST - epublish
SO  - Front Endocrinol (Lausanne). 2021 Oct 21;12:738848. doi: 
      10.3389/fendo.2021.738848. eCollection 2021.