Evidence map›Paper›PMID 39017631›Full record

ReviewAmerican journal of hypertension2024

State-of-the-Art-Review: Mechanisms of Action of SGLT2 Inhibitors and Clinical Implications.

Volker Vallon

Abstract readReview
PubMed Full text at PMC Publisher
In one paragraph

Review in American journal of hypertension, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
49citing papers in PubMed, 2 pooled it
–field-weighted citation impact
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

49 citing papers in PubMed, 2 syntheses or guidelines pooled it.

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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

1 author.

Volker VallonDivision of Nephrology and Hypertension, Department of Medicine, University of California San Diego, La Jolla, California, USA.ORCID 0000-0002-9211-2063

Funding

UAB-UCSD O'Brien Center for Acute Kidney Injury ResearchU54DK137307 · UNIVERSITY OF ALABAMA AT BIRMINGHAM · 2025 to 2025
$872k
Glomerular and Tubular Function in the Recovering KidneyR01DK132690 · NIDDK · VETERANS MEDICAL RESEARCH FDN/SAN DIEGO · 2024 to 2025
$814k
Significance of Tubuloglomerular Feedback in SGLT1 and SGLT2 Inhibition in Diabetic Kidney DiseaseR01DK134616 · NIDDK · BOSTON MEDICAL CENTER · 2024 to 2025
$770k
Glomerular and Tubular Function in the Diabetic KidneyR01DK112042 · VETERANS MEDICAL RESEARCH FDN/SAN DIEGO · 2025 to 2025
$475k
NIA NIH HHS RF1 AG061296NIDDK NIH HHS R01 DK112042NIDDK NIH HHS R01 DK132690NIDDK NIH HHS R01 DK134616NIDDK NIH HHS U54 DK137307NIH HHS R01 DK112042University of Alabama at Birmingham/University of California-San Diego O'Brien Center of Acute Kidney Injury NIH P54 DK137307VA
6 · The paper itself

Abstract

backgroundInhibitors of the Na+-coupled glucose transporter SGLT2 (SGLT2i) primarily shift the reabsorption of large amounts of glucose from the kidney's early proximal tubule to downstream tubular segments expressing SGLT1, and the non-reabsorbed glucose is spilled into the urine together with some osmotic diuresis. How can this protect the kidneys and heart from failing as observed in individuals with and without type 2 diabetes? GOAL: Mediation analyses identified clinical phenotypes of SGLT2i associated with improved kidney and heart outcome, including a reduction of plasma volume or increase in hematocrit, and lowering of serum urate levels and albuminuria. This review outlines how primary effects of SGLT2i on the early proximal tubule can explain these phenotypes.

resultsThe physiology of tubule-glomerular communication provides the basis for acute lowering of GFR and glomerular capillary pressure, which contributes to lowering of albuminuria but also to long term preservation of GFR, at least in part by reducing kidney cortex oxygen demand. Functional co-regulation of SGLT2 with other sodium and metabolite transporters in the early proximal tubule explains why SGLT2i initially excrete more sodium than expected and are uricosuric, thereby reducing plasma volume and serum urate. Inhibition of SGLT2 reduces early proximal tubule gluco-toxicity and by shifting transport downstream may simulate "systemic hypoxia", and the resulting increase in erythropoiesis, together with the osmotic diuresis, enhances hematocrit and improves blood oxygen delivery. Cardio-renal protection by SGLT2i is also provided by a fasting-like and insulin-sparing metabolic phenotype and, potentially, by off-target effects on the heart and microbiotic formation of uremic toxins.

Indexed as

Diabetes Mellitus, Type 2Kidney Tubules, ProximalSodium-Glucose Transporter 2 InhibitorsAnimalsBlood GlucoseGlomerular Filtration RateHumansSodium-Glucose Transporter 2Treatment OutcomeBlood GlucoseSodium-Glucose Transporter 2Sodium-Glucose Transporter 2 Inhibitorsblood pressurefastingGFRgliflozinhypertensionnatriuresisproximal tubuleuremic toxins

Identifiers

PMID39017631
PMCPMC11471837

What Socratic holds

Textmetadata
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.