Evidence map›Paper›PMID 26861783›Full record

ArticleDiabetes2016

Shift to Fatty Substrate Utilization in Response to Sodium-Glucose Cotransporter 2 Inhibition in Subjects Without Diabetes and Patients With Type 2 Diabetes.

Ele Ferrannini, Simona Baldi, Silvia Frascerra, Brenno Astiarraga, Tim Heise, Roberto Bizzotto, Andrea Mari, Thomas R Pieber, Elza Muscelli

3 registry-linked trialsAbstract readComparative StudyControlled Clinical TrialMulticenter Study
PubMed Publisher
In one paragraph

Article in Diabetes, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 3 registered trials, which are not on this map. Cited by 383 papers, 6 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
383citing papers in PubMed, 6 pooled it
38.6field-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.

NCT03151343 phase3completedstarted 2017, after this paper: background citation

Effects of SGLT-2 Inhibitor on Myocardial Perfusion, Function and Metabolism in Type 2 DM Patients at High Cardiovascular Risk: The SIMPle Randomized Clinical Trial

Ran2017Enrolled92Registered outcomes22Posted comparisons0ConditionsType2 Diabetes MellitusArmsempagliflozin, Placebo Oral Tablet
PMID 24948511PMID 24463454PMID 23219297PMID 23524053PMID 24176441PMID 24449227PMID 25344694PMID 25402275PMID 25616707PMID 25755288PMID 25921853PMID 26378978other papers from this trial
Open the trial in the graph
NCT05719714 phase1 / phase2active not recruitingstarted 2024, after this paper: background citation

Effect of Dapagliflozin on Metabolomics and Cardiac Mechanics in Chronic Kidney Disease

Ran2024Enrolled18Registered outcomes5Posted comparisons0ConditionsChronic Kidney Diseases, Heart Failure, Heart Failure With Preserved Ejection Fraction, Kidney DiseasesArmsDapagliflozin 10 MG [Farxiga]
PMID 29166232PMID 29526832PMID 29133604PMID 27289124PMID 26981940PMID 26050125PMID 25533966PMID 25370599PMID 24218128PMID 21817129PMID 21262990PMID 18760751other papers from this trial
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NCT05512130 early_phase1unknown statusnot on this mapstarted 2022, after this paper: background citation

Sodium-Glucose Cotransporter-2 Inhibitors: A Potential Novel Treatment for Epilepsy

TypeinterventionalSponsorWashington University School of MedicineRan2022 to 2023Enrolled18ConditionsEpilepsyArmsEmpagliflozin 25 mg, Placebo
3 · Its place in the literature

Who cites it

383 citing papers in PubMed, 6 syntheses or guidelines pooled it, 701 citations in OpenAlex.

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323 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

9 authors at 4 institutions in 3 countries.

Ele FerranniniCNR Institute of Clinical Physiology, Pisa, Italy Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy ferranni@ifc.cnr.it.
Simona BaldiDepartment of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.
Silvia FrascerraDepartment of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.
Brenno AstiarragaDepartment of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.
Tim HeiseProfil, Neuss, Germany.
Roberto BizzottoCNR Institute of Neurosciences, Padua, Italy.
Andrea MariCNR Institute of Neurosciences, Padua, Italy.
Thomas R PieberDivision of Endocrinology and Metabolism, Department of Internal Medicine, Medical University of Graz, Graz, Austria.
Elza MuscelliDepartment of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.
University of Pisa · ITNeuroscience Institute · ITMedical University of Graz · ATProfil Institute for Metabolic Research · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Pharmacologically induced glycosuria elicits adaptive responses in glucose homeostasis and hormone release. In type 2 diabetes (T2D), along with decrements in plasma glucose and insulin levels and increments in glucagon release, sodium-glucose cotransporter 2 (SGLT2) inhibitors induce stimulation of endogenous glucose production (EGP) and a suppression of tissue glucose disposal (TGD). We measured fasting and postmeal glucose fluxes in 25 subjects without diabetes using a double glucose tracer technique; in these subjects and in 66 previously reported patients with T2D, we also estimated lipolysis (from [(2)H5]glycerol turnover rate and circulating free fatty acids, glycerol, and triglycerides), lipid oxidation (LOx; by indirect calorimetry), and ketogenesis (from circulating β-hydroxybutyrate concentrations). In both groups, empagliflozin administration raised EGP, lowered TGD, and stimulated lipolysis, LOx, and ketogenesis. The pattern of glycosuria-induced changes was similar in subjects without diabetes and in those with T2D but quantitatively smaller in the former. With chronic (4 weeks) versus acute (first dose) drug administration, glucose flux responses were attenuated, whereas lipid responses were enhanced; in patients with T2D, fasting β-hydroxybutyrate levels rose from 246 ± 288 to 561 ± 596 µmol/L (P < 0.01). We conclude that by shunting substantial amounts of carbohydrate into urine, SGLT2-mediated glycosuria results in a progressive shift in fuel utilization toward fatty substrates. The associated hormonal milieu (lower insulin-to-glucagon ratio) favors glucose release and ketogenesis.

Indexed as

Sodium-Glucose Transporter 2 Inhibitors3-Hydroxybutyric AcidAlgorithmsBenzhydryl CompoundsCarbohydrate MetabolismC-Reactive ProteinDiabetes Mellitus, Type 2Energy MetabolismGlucagonGlucagon-Like Peptide 1Glucose IntoleranceGlucosidesGlycosuriaHumansHypoglycemic AgentsInsulin3-Hydroxybutyric AcidBenzhydryl CompoundsC-Reactive ProteinempagliflozinGlucagonGlucagon-Like Peptide 1GlucosidesHypoglycemic AgentsInsulinMembrane Transport ModulatorsSLC5A2 protein, humanSodium-Glucose Transporter 2Sodium-Glucose Transporter 2 Inhibitors

Identifiers

PMID26861783
OpenAlexW2341611738

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.