Evidence mapPaperPMID 41469882Full record

Trial reportCardiovascular diabetology2025

Dapagliflozin modulates plasma lipidomic profile and urinary metabolite excretion in type 2 diabetes.

Samantha Pezzica, Filippo Pratesi, Silvia Sabatini, Fabrizia Carli, Alessandro Mengozzi, Anna Solini, Amalia Gastaldelli

Abstract readRandomized Controlled Trial
In one paragraph

Trial report in Cardiovascular diabetology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
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

1 citing paper in PubMed.

  1. Article
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

7 authors.

Samantha PezzicaNational Research Council (CNR), Institute of Clinical Physiology (IFC), Pisa, Italy.ORCID http://orcid.org/0000-0003-1285-4946
Filippo PratesiNational Research Council (CNR), Institute of Clinical Physiology (IFC), Pisa, Italy.ORCID http://orcid.org/0000-0002-5441-1257
Silvia SabatiniNational Research Council (CNR), Institute of Clinical Physiology (IFC), Pisa, Italy.ORCID http://orcid.org/0000-0003-3251-4412
Fabrizia CarliNational Research Council (CNR), Institute of Clinical Physiology (IFC), Pisa, Italy.ORCID http://orcid.org/0000-0003-2540-1110
Alessandro MengozziDepartment of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.ORCID http://orcid.org/0000-0003-2834-9725
Anna Solini *Department of Surgical, Medical, Molecular and Critical Area Pathology, University of Pisa, Pisa, Italy.ORCID http://orcid.org/0000-0002-7855-8253
Amalia Gastaldelli *National Research Council (CNR), Institute of Clinical Physiology (IFC), Pisa, Italy. amalia.gastaldelli@cnr.it.ORCID http://orcid.org/0000-0003-2594-1651

Funding

Horizon 2020 Framework Programme Project PAS GRAS, grant# 101080329Ministero dell'Istruzione, dell'Università e della Ricerca PRIN 2017: 20175L9H7HMinistero dell'Istruzione, dell'Università e della Ricerca PRIN 2017: 20178YTNWC
6 · The paper itself

Abstract

backgroundDapagliflozin (DAPA) has shown major nephroprotective effects, improving kidney metabolism and oxigenation. Lipidomics and metabolomics are powerful tools for understanding such effects, providing a comprehensive look at how SGLT2 inhibitors might change the metabolic landscape beyond their primary glucose-lowering action. We investigated changes in plasma metabolomic/lipidomic profile and urinary excretion of metabolites that could occur independent of increased diuresis.

methodsA two-armed, parallel-design, randomized clinical trial was conducted in subjects with type 2 diabetes and hypertension who received treatment with DAPA 10 mg/day or hydrochlorothiazide 12.5 mg/day for four weeks. Lipidomics and metabolomics were performed by high resolution mass spectrometry in fasting plasma and 24-hour urine samples collected before and after treatment.

resultsCompared to hydrochlorothiazide, DAPA significantly increased plasma isoleucine, methionine, citrate, β-hydroxybutyrate and decreased lactate. DAPA induced plasma lipid remodeling towards a significant raise in free fatty acids (FFAs) and some sphingomyelins and lysophosphatidylcholines containing these fatty acids. A significant change was observed in plasma medium- and short-chain acylcarnitines, positively correlated with changes in plasma FFAs and β-hydroxybutyrate. In addition, DAPA, but not hydrochlorothiazide, significantly increased 24-h urinary excretion of several amino-acids, lactate, TCA cycle metabolites, β-hydroxybutyrate and electrolytes, except for a decrease in malate excretion.

conclusionsDAPA treatment has major effects on the plasma lipidomic and the urine metabolomic profiles, with significant increased renal excretion of several metabolites, especially amino-acids, independently of increased diuresis. These data offer insights into the complex metabolic pathways leading to kidney protection by SGLT2 inhibitors. CLINICAL TRIAL INFORMATION: European Union Drug Regulating Authorities Clinical Trials No. 2015-004164-11.

Indexed as

Antihypertensive AgentsBenzhydryl CompoundsDiabetes Mellitus, Type 2GlucosidesHypertensionLipid MetabolismLipidomicsLipidsRenal EliminationSodium-Glucose Transporter 2 InhibitorsAgedBiomarkersBlood GlucoseFemaleHumansHydrochlorothiazideAntihypertensive AgentsBenzhydryl CompoundsBiomarkersBlood GlucosedapagliflozinGlucosidesHydrochlorothiazideLipidsSodium-Glucose Transporter 2 InhibitorsHydrochlorothiazideKidneyLipidomicMetabolomicSGLT2 inhibitorsType 2 diabetes

Identifiers

PMID41469882
PMCPMC12860147

What Socratic holds

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Registered trials

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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.