Dapagliflozin added to metformin reduces perirenal fat layer in type 2 diabetic patients with obesity

Sodium-glucose co-transporters type 2 inhibitors (SLGT2i) are highly effective in controlling type 2 diabetes, but reported beneficial cardiovascular effects suggest broader actions on insulin resistance. Weight loss may be initially explained by glycosuria-induced net caloric output and secondary v...

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Autores: Cuatrecasas Cambra, Guillem, De Cabo, Francisco, Coves, M. José, Patrascioiu, Ioana, Aguilar, Gerardo, Cuatrecasas Cambra, Gabriel, March, Sonia, Calbo, Marta, Rossell, Olga, Balfegó, Mariona, Benito, Camila, Di Gregorio, Silvana, Garcia-Lorda, Pilar, Marron, Elena M
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2024
País:España
Institución:Universitat Oberta de Catalunya (UOC)
Repositorio:O2, repositorio institucional de la UOC
OAI Identifier:oai:openaccess.uoc.edu:10609/152095
Acceso en línea:http://hdl.handle.net/10609/152095
https://doi.org/10.1038/s41598-024-61590-6
Access Level:acceso abierto
Palabra clave:ultrasound
dapaglifozin
metformin
preperitoneal fat
omental fat
perirenal fat
metabolic syndrome
cardiovascular risk
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spelling Dapagliflozin added to metformin reduces perirenal fat layer in type 2 diabetic patients with obesityCuatrecasas Cambra, GuillemDe Cabo, FranciscoCoves, M. JoséPatrascioiu, IoanaAguilar, GerardoCuatrecasas Cambra, GabrielMarch, SoniaCalbo, MartaRossell, OlgaBalfegó, MarionaBenito, CamilaDi Gregorio, SilvanaGarcia-Lorda, PilarMarron, Elena Multrasounddapaglifozinmetforminpreperitoneal fatomental fatperirenal fatmetabolic syndromecardiovascular riskSodium-glucose co-transporters type 2 inhibitors (SLGT2i) are highly effective in controlling type 2 diabetes, but reported beneficial cardiovascular effects suggest broader actions on insulin resistance. Weight loss may be initially explained by glycosuria-induced net caloric output and secondary volumetric reduction, but its maintenance could be due to loss of visceral fat mass. Structured ultrasound (US) imaging of abdominal adipose tissue (“eco-obesity”) is a recently described methodology used to measure 5 consecutive layers of abdominal fat, not assessable by DEXA or CT scan: superficial subcutaneous (SS), deep subcutaneous (DS), preperitoneal (PP), omental (Om) and right perirenal (RK). PP, Om and RK are predictors of metabolic syndrome (MS) with defined cut-off points. To assess the effect of SLGT2i on every fat depot we enrolled 29 patients with type 2 Diabetes (HbA1c 6.5–9%) and Obesity (IMC > 30 kg/m2) in an open-label, randomized, phase IV trial (EudraCT: 2019-000979-16): the Omendapa trial. Diabetes was diagnosed < 12 months before randomization and all patients were treatment naïve. 14 patients were treated with metformin alone (cohort A) and 15 were treated with metformin + dapaglifozin (cohort B). Anthropometric measures and laboratory tests for glucose, lipid profile, insulin, HOMA, leptin, ultrasensitive-CRP and microalbuminuria (MAL) were done at baseline, 3rd and 6th months. At 6th month, weight loss was −5.5 ± 5.2 kg (5.7% from initial weight) in cohort A and −8.4 ± 4.4 kg (8.6%) in cohort B. Abdominal circumference showed a −2.7 ± 3.1 cm and −5.4 ± 2.5 cm reduction, respectively (p = 0.011). Both Metformin alone (−19.4 ± 20.1 mm; −21.7%) or combined with Dapaglifozin (−20.5 ± 19.4 mm; −21.8%) induced significant Om fat reduction. 13.3% of cohort A patients and 21.4% of cohort’s B reached Om thickness below the cut-off for MS criteria. RK fat loss was significantly greater in cohort B group compared to cohort A, at both kidneys. Only in the Met + Dapa group, we observed correlations between Om fat with leptin/CRP/MAL and RK fat with HOMA-IR. US is a useful clinical tool to assess ectopic fat depots. Both Metformin and Dapaglifozin induce fat loss in layers involved with MS but combined treatment is particularly effective in perirenal fat layer reduction. Perirenal fat should be considered as a potential target for cardiovascular dapaglifozin beneficial effects.Nature Publishing Group202520252024info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfapplication/pdfhttp://hdl.handle.net/10609/152095https://doi.org/10.1038/s41598-024-61590-6reponame:O2, repositorio institucional de la UOCinstname:Universitat Oberta de Catalunya (UOC)InglésScientific Reports, 2024, 14(1)https://www.nature.com/articles/s41598-024-61590-6info:eu-repo/grantAgreement/ESR-17–12784//CC BYhttp://creativecommons.org/licenses/by/3.0/es/info:eu-repo/semantics/openAccessoai:openaccess.uoc.edu:10609/1520952026-05-28T12:42:01Z
dc.title.none.fl_str_mv Dapagliflozin added to metformin reduces perirenal fat layer in type 2 diabetic patients with obesity
title Dapagliflozin added to metformin reduces perirenal fat layer in type 2 diabetic patients with obesity
spellingShingle Dapagliflozin added to metformin reduces perirenal fat layer in type 2 diabetic patients with obesity
Cuatrecasas Cambra, Guillem
ultrasound
dapaglifozin
metformin
preperitoneal fat
omental fat
perirenal fat
metabolic syndrome
cardiovascular risk
title_short Dapagliflozin added to metformin reduces perirenal fat layer in type 2 diabetic patients with obesity
title_full Dapagliflozin added to metformin reduces perirenal fat layer in type 2 diabetic patients with obesity
title_fullStr Dapagliflozin added to metformin reduces perirenal fat layer in type 2 diabetic patients with obesity
title_full_unstemmed Dapagliflozin added to metformin reduces perirenal fat layer in type 2 diabetic patients with obesity
title_sort Dapagliflozin added to metformin reduces perirenal fat layer in type 2 diabetic patients with obesity
dc.creator.none.fl_str_mv Cuatrecasas Cambra, Guillem
De Cabo, Francisco
Coves, M. José
Patrascioiu, Ioana
Aguilar, Gerardo
Cuatrecasas Cambra, Gabriel
March, Sonia
Calbo, Marta
Rossell, Olga
Balfegó, Mariona
Benito, Camila
Di Gregorio, Silvana
Garcia-Lorda, Pilar
Marron, Elena M
author Cuatrecasas Cambra, Guillem
author_facet Cuatrecasas Cambra, Guillem
De Cabo, Francisco
Coves, M. José
Patrascioiu, Ioana
Aguilar, Gerardo
Cuatrecasas Cambra, Gabriel
March, Sonia
Calbo, Marta
Rossell, Olga
Balfegó, Mariona
Benito, Camila
Di Gregorio, Silvana
Garcia-Lorda, Pilar
Marron, Elena M
author_role author
author2 De Cabo, Francisco
Coves, M. José
Patrascioiu, Ioana
Aguilar, Gerardo
Cuatrecasas Cambra, Gabriel
March, Sonia
Calbo, Marta
Rossell, Olga
Balfegó, Mariona
Benito, Camila
Di Gregorio, Silvana
Garcia-Lorda, Pilar
Marron, Elena M
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv ultrasound
dapaglifozin
metformin
preperitoneal fat
omental fat
perirenal fat
metabolic syndrome
cardiovascular risk
topic ultrasound
dapaglifozin
metformin
preperitoneal fat
omental fat
perirenal fat
metabolic syndrome
cardiovascular risk
description Sodium-glucose co-transporters type 2 inhibitors (SLGT2i) are highly effective in controlling type 2 diabetes, but reported beneficial cardiovascular effects suggest broader actions on insulin resistance. Weight loss may be initially explained by glycosuria-induced net caloric output and secondary volumetric reduction, but its maintenance could be due to loss of visceral fat mass. Structured ultrasound (US) imaging of abdominal adipose tissue (“eco-obesity”) is a recently described methodology used to measure 5 consecutive layers of abdominal fat, not assessable by DEXA or CT scan: superficial subcutaneous (SS), deep subcutaneous (DS), preperitoneal (PP), omental (Om) and right perirenal (RK). PP, Om and RK are predictors of metabolic syndrome (MS) with defined cut-off points. To assess the effect of SLGT2i on every fat depot we enrolled 29 patients with type 2 Diabetes (HbA1c 6.5–9%) and Obesity (IMC > 30 kg/m2) in an open-label, randomized, phase IV trial (EudraCT: 2019-000979-16): the Omendapa trial. Diabetes was diagnosed < 12 months before randomization and all patients were treatment naïve. 14 patients were treated with metformin alone (cohort A) and 15 were treated with metformin + dapaglifozin (cohort B). Anthropometric measures and laboratory tests for glucose, lipid profile, insulin, HOMA, leptin, ultrasensitive-CRP and microalbuminuria (MAL) were done at baseline, 3rd and 6th months. At 6th month, weight loss was −5.5 ± 5.2 kg (5.7% from initial weight) in cohort A and −8.4 ± 4.4 kg (8.6%) in cohort B. Abdominal circumference showed a −2.7 ± 3.1 cm and −5.4 ± 2.5 cm reduction, respectively (p = 0.011). Both Metformin alone (−19.4 ± 20.1 mm; −21.7%) or combined with Dapaglifozin (−20.5 ± 19.4 mm; −21.8%) induced significant Om fat reduction. 13.3% of cohort A patients and 21.4% of cohort’s B reached Om thickness below the cut-off for MS criteria. RK fat loss was significantly greater in cohort B group compared to cohort A, at both kidneys. Only in the Met + Dapa group, we observed correlations between Om fat with leptin/CRP/MAL and RK fat with HOMA-IR. US is a useful clinical tool to assess ectopic fat depots. Both Metformin and Dapaglifozin induce fat loss in layers involved with MS but combined treatment is particularly effective in perirenal fat layer reduction. Perirenal fat should be considered as a potential target for cardiovascular dapaglifozin beneficial effects.
publishDate 2024
dc.date.none.fl_str_mv 2024
2025
2025
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10609/152095
https://doi.org/10.1038/s41598-024-61590-6
url http://hdl.handle.net/10609/152095
https://doi.org/10.1038/s41598-024-61590-6
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Scientific Reports, 2024, 14(1)
https://www.nature.com/articles/s41598-024-61590-6
info:eu-repo/grantAgreement/ESR-17–12784//
dc.rights.none.fl_str_mv CC BY
http://creativecommons.org/licenses/by/3.0/es/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv CC BY
http://creativecommons.org/licenses/by/3.0/es/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Nature Publishing Group
publisher.none.fl_str_mv Nature Publishing Group
dc.source.none.fl_str_mv reponame:O2, repositorio institucional de la UOC
instname:Universitat Oberta de Catalunya (UOC)
instname_str Universitat Oberta de Catalunya (UOC)
reponame_str O2, repositorio institucional de la UOC
collection O2, repositorio institucional de la UOC
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