Evidence mapPaperPMID 32827269Full record

Trial reportDiabetologia2020

Increase in endogenous glucose production with SGLT2 inhibition is attenuated in individuals who underwent kidney transplantation and bilateral native nephrectomy.

Giuseppe Daniele, Carolina Solis-Herrera, Angela Dardano, Andrea Mari, Andrea Tura, Laura Giusti, Jancy J Kurumthodathu, Beatrice Campi, Alessandro Saba, Anna Maria Bianchi and 5 more

Registry-linked trialOpen access · hybridAbstract readRandomized Controlled Trial
In one paragraph

Trial report in Diabetologia, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It reports registered trial NCT03168295. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
2.6field-weighted citation impact, top 9% 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.

NCT03168295 phase4completed

SGLT2 INHIBITION AND STIMULATIION OF ENDOGENOUS GLUCOSE PRODUCTION Significance - PROTOCOL 3: Role of the Renal Nerves in the Increase in EGP in Response to Glucosuria

Ran2016Enrolled34Registered outcomes3Posted comparisons0ConditionsDiabetes Mellitus, Type 2ArmsDapagliflozin 10mg then Placebo Oral Tablet, Placebo Oral Tablet then Dapagliflozin 10mg
Open the trial in the graph
3 · Its place in the literature

Who cites it

13 citing papers in PubMed, 32 citations in OpenAlex.

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  6. SGLT2 inhibitors: cardiorenal metabolic drugs for the ages.The Journal of clinical investigation · 2024
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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

15 authors at 3 institutions in 2 countries.

Giuseppe DanieleDepartment of Clinical and Experimental Medicine, Section of Metabolic Diseases and Diabetes, University of Pisa, Via Paradisa 2, 56124, Pisa, Italy.ORCID 0000-0001-6301-9161
Carolina Solis-HerreraDivision of Diabetes, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.
Angela DardanoDepartment of Clinical and Experimental Medicine, Section of Metabolic Diseases and Diabetes, University of Pisa, Via Paradisa 2, 56124, Pisa, Italy.
Andrea MariMetabolic Unit, CNR Institute of Neuroscience, Padova, Italy.
Andrea TuraMetabolic Unit, CNR Institute of Neuroscience, Padova, Italy.
Laura GiustiDepartment of Clinical and Experimental Medicine, Section of Metabolic Diseases and Diabetes, University of Pisa, Via Paradisa 2, 56124, Pisa, Italy.
Jancy J KurumthodathuDepartment of Clinical and Experimental Medicine, Section of Metabolic Diseases and Diabetes, University of Pisa, Via Paradisa 2, 56124, Pisa, Italy.
Beatrice CampiDepartment of Clinical and Experimental Medicine, Section of Metabolic Diseases and Diabetes, University of Pisa, Via Paradisa 2, 56124, Pisa, Italy.
Alessandro SabaDepartment of Clinical and Experimental Medicine, Section of Metabolic Diseases and Diabetes, University of Pisa, Via Paradisa 2, 56124, Pisa, Italy.
Anna Maria BianchiDepartment of Clinical and Experimental Medicine, Section of Metabolic Diseases and Diabetes, University of Pisa, Via Paradisa 2, 56124, Pisa, Italy.
Carla TregnaghiDepartment of Clinical and Experimental Medicine, Section of Metabolic Diseases and Diabetes, University of Pisa, Via Paradisa 2, 56124, Pisa, Italy.
Maria Francesca EgidiDepartment of Clinical and Experimental Medicine, Section of Metabolic Diseases and Diabetes, University of Pisa, Via Paradisa 2, 56124, Pisa, Italy.
Muhammad Abdul-GhaniDivision of Diabetes, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.
Ralph DeFronzoDivision of Diabetes, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.
Stefano Del PratoDepartment of Clinical and Experimental Medicine, Section of Metabolic Diseases and Diabetes, University of Pisa, Via Paradisa 2, 56124, Pisa, Italy. stefano.delprato@med.unipi.it.ORCID 0000-0002-5388-0270
University of Pisa · ITThe University of Texas Health Science Center at San Antonio · USNeuroscience Institute · IT

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

aims/hypothesisThe glucosuria induced by sodium-glucose cotransporter 2 (SGLT2) inhibition stimulates endogenous (hepatic) glucose production (EGP), blunting the decline in HbA

methodsThis was a parallel, randomised, double-blind, placebo-controlled, single-centre study, designed to evaluate the effect of a single dose of dapagliflozin or placebo on EGP determined by stable-tracer technique. We recruited non-diabetic individuals who were 30-65 years old, with a BMI of 25-35 kg/m

resultsTwenty non-diabetic renal transplant patients (ten with residual native kidneys, ten with bilateral nephrectomy) participated in the study. Dapagliflozin induced greater glucosuria in individuals with residual native kidneys vs nephrectomised individuals (8.6 ± 1.1 vs 5.5 ± 0.5 g/6 h; p = 0.02; data not shown). During the 6 h study period, plasma glucose decreased only slightly and similarly in both groups, with no difference compared with placebo (data not shown). Following administration of placebo, there was a progressive time-related decline in EGP that was similar in both nephrectomised individuals and individuals with residual native kidneys. Following dapagliflozin administration, EGP declined in both groups, but the differences between the decrement in EGP with dapagliflozin and placebo in the group with bilateral nephrectomy (Δ = 1.11 ± 0.72 μmol min CONCLUSIONS/

interpretationIn nephrectomised individuals, the hepatic compensatory response to acute SGLT2 inhibitor-induced glucosuria was attenuated, as compared with individuals with residual native kidneys, suggesting that SGLT2 inhibitor-mediated stimulation of hepatic glucose production via efferent renal nerves occurs in an attempt to compensate for the urinary glucose loss (i.e. a renal-hepatic axis).

trial registrationClinicalTrials.gov NCT03168295

fundingThis protocol was supported by Qatar National Research Fund (QNRF) Award No. NPRP 8-311-3-062 and NIH grant DK024092-38. Graphical abstract.

Indexed as

AdultAgedDouble-Blind MethodGlucoseGlycated HemoglobinHumansKidney TransplantationMiddle AgedNephrectomySodium-Glucose Transporter 2GlucoseGlycated Hemoglobinhemoglobin A1c protein, humanSodium-Glucose Transporter 2DapagliflozinEndogenous glucose productionGlucosuria

Identifiers

PMID32827269
PMCPMC7527374
OpenAlexW3080756519

What Socratic holds

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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 Socratic graph.