Evidence mapPaperPMID 34745006Full record

ReviewFrontiers in endocrinology2021

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

Soraya Puglisi, Alessandro Rossini, Roberta Poli, Francesca Dughera, Anna Pia, Massimo Terzolo, Giuseppe Reimondo

Open access · goldAbstract readReview
In one paragraph

Review in Frontiers in endocrinology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 72 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
72citing papers in PubMed, 2 pooled it
11.4field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

72 citing papers in PubMed, 2 syntheses or guidelines pooled it, 122 citations in OpenAlex.

  1. Comparing GLP-1 agonists versus other weight loss interventions on risk of atrial fibrillation recurrence after catheter ablation: a meta-analysis.Journal of interventional cardiac electrophysiology : an international journal of arrhythmias and pacing · 2026
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12 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 3 institutions in 1 country.

Soraya PuglisiInternal Medicine, Department of Clinical and Biological Sciences, San Luigi Gonzaga Hospital, University of Turin, Orbassano, Italy.
Alessandro RossiniEndocrinology and Diabetes Unit, ASST Papa Giovanni XXIII, Bergamo, Italy.
Roberta PoliMetabolic Disease and Diabetes Unit, San Luigi Gonzaga Hospital, Orbassano, Italy.
Francesca DugheraInternal Medicine, Department of Clinical and Biological Sciences, San Luigi Gonzaga Hospital, University of Turin, Orbassano, Italy.
Anna PiaInternal Medicine, Department of Clinical and Biological Sciences, San Luigi Gonzaga Hospital, University of Turin, Orbassano, Italy.
Massimo TerzoloInternal Medicine, Department of Clinical and Biological Sciences, San Luigi Gonzaga Hospital, University of Turin, Orbassano, Italy.
Giuseppe ReimondoInternal Medicine, Department of Clinical and Biological Sciences, San Luigi Gonzaga Hospital, University of Turin, Orbassano, Italy.
Ospedale San Luigi Gonzaga · ITUniversity of Turin · ITOspedale Papa Giovanni XXIII · IT

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

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.

Indexed as

Glucagon-Like Peptide-1 Receptor AgonistsAldosteroneBlood GlucoseHumansReninRenin-Angiotensin SystemSodium-Glucose Transporter 2 InhibitorsAldosteroneBlood GlucoseGlucagon-Like Peptide-1 Receptor AgonistsReninSodium-Glucose Transporter 2 Inhibitorsaldosteronecardiovascular diseasecardiovascular riskdiabetes mellitus type 2diabetic kidney diseaseglucagon-like peptide-1 receptor agonistreninsodium-glucose cotransporter-2 inhibitor

Identifiers

PMID34745006
PMCPMC8567993
OpenAlexW3208624876

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.