Evidence mapPaperPMID 39078489Full record

Trial reportDiabetologia2024

Effects of semaglutide, empagliflozin and their combination on renal diffusion-weighted MRI and total kidney volume in patients with type 2 diabetes: a post hoc analysis from a 32 week randomised trial.

Liv Vernstrøm, Søren Gullaksen, Steffen S Sørensen, Steffen Ringgaard, Christoffer Laustsen, Henrik Birn, Kristian L Funck, Esben Laugesen, Per L Poulsen

Abstract readRandomized Controlled Trial
In one paragraph

Trial report in Diabetologia, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
5citing 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

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

  1. Pooled it
  2. Pooled it
  3. Trial
  4. Trial
  5. Review
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.

Liv VernstrømDepartment of Clinical Medicine, Aarhus University, Aarhus, Denmark. lvh@clin.au.dk.ORCID http://orcid.org/0000-0003-2875-435X
Søren GullaksenDepartment of Clinical Medicine, Aarhus University, Aarhus, Denmark.ORCID http://orcid.org/0000-0001-8275-1278
Steffen S SørensenDepartment of Clinical Medicine, Aarhus University, Aarhus, Denmark.
Steffen RinggaardThe MR Research Centre, Aarhus University, Aarhus, Denmark.ORCID http://orcid.org/0000-0001-5353-7379
Christoffer LaustsenThe MR Research Centre, Aarhus University, Aarhus, Denmark.ORCID http://orcid.org/0000-0002-0317-2911
Henrik BirnDepartment of Clinical Medicine, Aarhus University, Aarhus, Denmark.ORCID http://orcid.org/0000-0003-3715-7266
Kristian L FunckSteno Diabetes Center, Aarhus University Hospital, Aarhus, Denmark.ORCID http://orcid.org/0000-0003-0213-5550
Esben Laugesen *Steno Diabetes Center, Aarhus University Hospital, Aarhus, Denmark.ORCID http://orcid.org/0000-0003-1782-1596
Per L Poulsen *Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.ORCID http://orcid.org/0000-0001-6468-2715

Funding

Health Research Fund of Central Denmark Region A3192Lægeforeningen 2019-3780/41Novo Nordisk Fonden NNF170C0029064
6 · The paper itself

Abstract

aims/hypothesisThe apparent diffusion coefficient (ADC) derived from diffusion-weighted MRI (DWI-MRI) has been proposed as a measure of changes in kidney microstructure, including kidney fibrosis. In advanced kidney disease, the kidneys often become atrophic; however, in the initial phase of type 2 diabetes, there is an increase in renal size. Glucagon-like peptide-1 receptor agonists and sodium-glucose cotransporter 2 inhibitors both provide protection against progression of kidney disease in diabetes. However, the mechanisms are incompletely understood. To explore this, we examined the effects of semaglutide, empagliflozin and their combination on renal ADC and total kidney volume (TKV).

methodsThis was a substudy of a randomised clinical trial on the effects of semaglutide and empagliflozin alone or in combination. Eighty patients with type 2 diabetes and high risk of CVD were randomised into four groups (n=20 in each) receiving either tablet placebo, empagliflozin, a combination of semaglutide and tablet placebo (herein referred to as the 'semaglutide' group), or the combination of semaglutide and empagliflozin (referred to as the 'combination-therapy' group). The semaglutide and the combination-therapy group had semaglutide treatment for 16 weeks and then had either tablet placebo or empagliflozin added to the treatment, respectively, for a further 16 weeks; the placebo and empagliflozin groups were treated with the respective monotherapy for 32 weeks. We analysed the effects of treatment on changes in ADC (cortical, medullary and the cortico-medullary difference [ΔADC; medullary ADC subtracted from cortical ADC]), as well as TKV measured by MRI.

resultsBoth semaglutide and empagliflozin decreased cortical ADC significantly compared with placebo (semaglutide: -0.20×10 CONCLUSIONS/

interpretationIn a population with type 2 diabetes and high risk of CVD, semaglutide and empagliflozin significantly reduced cortical ADC compared with placebo, indicating microstructural changes in the kidneys. These changes were not associated with changes in GFR, albuminuria or inflammation. Further, we found a decrease in TKV in all active treatment groups, which was possibly mediated by a reduction in hyperfiltration. Our findings suggest that DWI-MRI may serve as a promising tool for investigating the underlying mechanisms of medical interventions in individuals with type 2 diabetes but may reflect effects not related to fibrosis.

trial registrationEuropean Union Drug Regulating Authorities Clinical Trials Database (EudraCT) 2019-000781-38.

Indexed as

Benzhydryl CompoundsDiabetes Mellitus, Type 2Glucagon-Like PeptidesGlucosidesKidneyAgedDiabetic NephropathiesDiffusion Magnetic Resonance ImagingDrug Therapy, CombinationFemaleHumansHypoglycemic AgentsMaleMiddle AgedSemaglutideSodium-Glucose Transporter 2 InhibitorsBenzhydryl CompoundsempagliflozinGlucagon-Like PeptidesGlucosidesHypoglycemic AgentsSemaglutideSodium-Glucose Transporter 2 InhibitorsApparent diffusion coefficientDiffusion-weighted magnetic resonance imagingGlucagon-like peptide-1 receptor agonistMagnetic resonance imagingSodium–glucose cotransporter 2 inhibitorsTotal kidney volumeType 2 diabetes

Identifiers

PMID39078489
PMCPMC11447057

What Socratic holds

Texttitle and abstract
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.