Evidence map›Paper›PMID 29371333›Full record

ReviewEuropean journal of endocrinology2018

MECHANISMS IN ENDOCRINOLOGY: SGLT2 inhibitors: clinical benefits by restoration of normal diurnal metabolism?

Russell L Esterline, Allan Vaag, Jan Oscarsson, Jiten Vora

Registry-linked trialAbstract readReview
PubMed Publisher
In one paragraph

Review in European journal of endocrinology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT05565976 (Dapagliflozin Effect in Cognitive Impairment in Stroke Trial), which is not on this map. Cited by 54 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
54citing papers in PubMed, 1 pooled it
8.1field-weighted citation impact, top 2% 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.

NCT05565976 phase2 / phase3unknown statusstarted 2020, after this paper: background citation

Dapagliflozin Effect in Cognitive Impairment in Stroke Trial

Ran2020Enrolled270Registered outcomes3Posted comparisons0ConditionsDementia, Vascular, Metabolic Syndrome, Mild Cognitive Impairment, Stroke, IschemicArmsAntidiabetic, Dapagliflozin 10mg Tab, Platelet Antiaggregant, Statins (Cardiovascular Agents)
PMID 33282811PMID 20204386PMID 23040716PMID 28095900PMID 28950419PMID 29016744PMID 29446769PMID 29573529PMID 31236801PMID 31248555PMID 31535829PMID 32115470other papers from this trial
Open the trial in the graph
3 · Its place in the literature

Who cites it

54 citing papers in PubMed, 1 synthesis or guideline pooled it, 95 citations in OpenAlex.

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  9. snoRNAs: New players in CKD biomarkers.Molecular therapy. Nucleic acids · 2026
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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

4 authors at 2 institutions in 2 countries.

Russell L EsterlineAstraZeneca Pharmaceuticals, Gaithersburg, Maryland, USA.
Allan VaagCardiovascular and Metabolic Disease (CVMD) Translational Medicine Unit, Early Clinical Development, IMED Biotech Unit, AstraZeneca, Gothenburg, Sweden.
Jan OscarssonAstraZeneca Pharmaceuticals, Gaithersburg, Maryland, USA.
Jiten VoraRoyal Liverpool University Hospital, University of Liverpool, Liverpool, UK.
AstraZeneca (Sweden) · SERoyal Liverpool University Hospital · GB

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Type 2 diabetes (T2D) is associated with inhibition of autophagic and lysosomal housekeeping processes that detrimentally affect key organ functioning; a process likely to be exacerbated by conventional insulin-driven anabolic therapies. We propose that the cardio-renal benefits demonstrated with sodium-glucose cotransporter-2 inhibitor (SGLT2i) treatment in T2D partly may be explained by their ability to drive consistent, overnight periods of increased catabolism brought about by constant glucosuria. Key steps driving this catabolic mechanism include: a raised glucagon/insulin ratio initially depleting glycogen in the liver and ultimately activating gluconeogenesis utilizing circulating amino acids (AAs); a general fuel switch from glucose to free fatty acids (accompanied by a change in mitochondrial morphology from a fission to a sustained fusion state driven by a decrease in AA levels); a decrease in circulating AAs and insulin driving inhibition of mammalian target of rapamycin complex 1 (mTORC1), which enhances autophagy/lysosomal degradation of dysfunctional organelles, eventually causing a change in mitochondrial morphology from a fission to a sustained fusion state. Resumption of eating in the morning restores anabolic biogenesis of new and fully functional organelles and proteins. Restoration of diurnal metabolic rhythms and flexibility by SGLT2is may have therapeutic implications beyond those already demonstrated for the cardio-renal axis and may therefore affect other non-diabetes disease states.

Indexed as

Sodium-Glucose Transporter 2 InhibitorsAnimalsCircadian RhythmDiabetes Mellitus, Type 2HumansHypoglycemic AgentsMetabolic DiseasesSodium-Glucose Transporter 2TOR Serine-Threonine KinasesHypoglycemic AgentsMTOR protein, humanSLC5A2 protein, humanSodium-Glucose Transporter 2Sodium-Glucose Transporter 2 InhibitorsTOR Serine-Threonine Kinases

Identifiers

PMID29371333
OpenAlexW2785119187

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

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 OpenQuestion graph.