The effect of liraglutide and sitagliptin on oxidative stress in persons with type 2 diabetes

Abstract Glucagon-like peptide 1 receptor agonists have shown cardioprotective effects which have been suggested to be mediated through inhibition of oxidative stress. We investigated the effect of treatment with a glucagon-like peptide 1 receptor agonist (liraglutide) on oxidative stress measured a...

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Autores principales:	Suvanjaa Sivalingam, Emil List Larsen, Daniel H. van Raalte, Marcel H. A. Muskiet, Mark M. Smits, Lennart Tonneijck, Jaap A. Joles, Bernt Johan von Scholten, Emilie Hein Zobel, Frederik Persson, Trine Henriksen, Lars Jorge Diaz, Tine W. Hansen, Henrik Enghusen Poulsen, Peter Rossing
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Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/3bcc699d77684b339336dcb21eb97295
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spelling	oai:doaj.org-article:3bcc699d77684b339336dcb21eb972952021-12-02T14:58:32ZThe effect of liraglutide and sitagliptin on oxidative stress in persons with type 2 diabetes10.1038/s41598-021-90191-w2045-2322https://doaj.org/article/3bcc699d77684b339336dcb21eb972952021-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-90191-whttps://doaj.org/toc/2045-2322Abstract Glucagon-like peptide 1 receptor agonists have shown cardioprotective effects which have been suggested to be mediated through inhibition of oxidative stress. We investigated the effect of treatment with a glucagon-like peptide 1 receptor agonist (liraglutide) on oxidative stress measured as urinary nucleic acid oxidation in persons with type 2 diabetes. Post-hoc analysis of two independent, randomised, placebo-controlled and double-blinded clinical trials. In a cross-over study where persons with type 2 diabetes and microalbuminuria (LIRALBU, n = 32) received liraglutide (1.8 mg/day) or placebo for 12 weeks in random order, separated by 4 weeks of wash-out. In a parallel-grouped study where obese persons with type 2 diabetes (SAFEGUARD, n = 56) received liraglutide (1.8 mg/day), sitagliptin (100 mg/day) or placebo for 12 weeks. Endpoints were changes in the urinary markers of DNA oxidation (8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodG)) and RNA oxidation [8-oxo-7,8-dihydroguanosine (8-oxoGuo)]. In LIRALBU, we observed no significant differences between treatment periods in urinary excretion of 8-oxodG [0.028 (standard error (SE): 0.17] nmol/mmol creatinine, p = 0.87) or of 8-oxoGuo [0.12 (0.12) nmol/mmol creatinine, p = 0.31]. In SAFEGUARD, excretion of 8-oxodG was not changed in the liraglutide group [2.8 (− 8.51; 15.49) %, p = 0.62] but a significant decline was demonstrated in the placebo group [12.6 (− 21.3; 3.1) %, p = 0.02], resulting in a relative increase in the liraglutide group compared to placebo (0.16 nmol/mmol creatinine, SE 0.07, p = 0.02). Treatment with sitagliptin compared to placebo demonstrated no significant difference (0.07 (0.07) nmol/mmol creatinine, p = 0.34). Nor were any significant differences for urinary excretion of 8-oxoGuo liraglutide vs placebo [0.09 (SE: 0.07) nmol/mmol creatinine, p = 0.19] or sitagliptin vs placebo [0.07 (SE: 0.07) nmol/mmol creatinine, p = 0.35] observed. This post-hoc analysis could not demonstrate a beneficial effect of 12 weeks of treatment with liraglutide or sitagliptin on oxidatively generated modifications of nucleic acid in persons with type 2 diabetes.Suvanjaa SivalingamEmil List LarsenDaniel H. van RaalteMarcel H. A. MuskietMark M. SmitsLennart TonneijckJaap A. JolesBernt Johan von ScholtenEmilie Hein ZobelFrederik PerssonTrine HenriksenLars Jorge DiazTine W. HansenHenrik Enghusen PoulsenPeter RossingNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-8 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Suvanjaa Sivalingam Emil List Larsen Daniel H. van Raalte Marcel H. A. Muskiet Mark M. Smits Lennart Tonneijck Jaap A. Joles Bernt Johan von Scholten Emilie Hein Zobel Frederik Persson Trine Henriksen Lars Jorge Diaz Tine W. Hansen Henrik Enghusen Poulsen Peter Rossing The effect of liraglutide and sitagliptin on oxidative stress in persons with type 2 diabetes
description	Abstract Glucagon-like peptide 1 receptor agonists have shown cardioprotective effects which have been suggested to be mediated through inhibition of oxidative stress. We investigated the effect of treatment with a glucagon-like peptide 1 receptor agonist (liraglutide) on oxidative stress measured as urinary nucleic acid oxidation in persons with type 2 diabetes. Post-hoc analysis of two independent, randomised, placebo-controlled and double-blinded clinical trials. In a cross-over study where persons with type 2 diabetes and microalbuminuria (LIRALBU, n = 32) received liraglutide (1.8 mg/day) or placebo for 12 weeks in random order, separated by 4 weeks of wash-out. In a parallel-grouped study where obese persons with type 2 diabetes (SAFEGUARD, n = 56) received liraglutide (1.8 mg/day), sitagliptin (100 mg/day) or placebo for 12 weeks. Endpoints were changes in the urinary markers of DNA oxidation (8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodG)) and RNA oxidation [8-oxo-7,8-dihydroguanosine (8-oxoGuo)]. In LIRALBU, we observed no significant differences between treatment periods in urinary excretion of 8-oxodG [0.028 (standard error (SE): 0.17] nmol/mmol creatinine, p = 0.87) or of 8-oxoGuo [0.12 (0.12) nmol/mmol creatinine, p = 0.31]. In SAFEGUARD, excretion of 8-oxodG was not changed in the liraglutide group [2.8 (− 8.51; 15.49) %, p = 0.62] but a significant decline was demonstrated in the placebo group [12.6 (− 21.3; 3.1) %, p = 0.02], resulting in a relative increase in the liraglutide group compared to placebo (0.16 nmol/mmol creatinine, SE 0.07, p = 0.02). Treatment with sitagliptin compared to placebo demonstrated no significant difference (0.07 (0.07) nmol/mmol creatinine, p = 0.34). Nor were any significant differences for urinary excretion of 8-oxoGuo liraglutide vs placebo [0.09 (SE: 0.07) nmol/mmol creatinine, p = 0.19] or sitagliptin vs placebo [0.07 (SE: 0.07) nmol/mmol creatinine, p = 0.35] observed. This post-hoc analysis could not demonstrate a beneficial effect of 12 weeks of treatment with liraglutide or sitagliptin on oxidatively generated modifications of nucleic acid in persons with type 2 diabetes.
format	article
author	Suvanjaa Sivalingam Emil List Larsen Daniel H. van Raalte Marcel H. A. Muskiet Mark M. Smits Lennart Tonneijck Jaap A. Joles Bernt Johan von Scholten Emilie Hein Zobel Frederik Persson Trine Henriksen Lars Jorge Diaz Tine W. Hansen Henrik Enghusen Poulsen Peter Rossing
author_facet	Suvanjaa Sivalingam Emil List Larsen Daniel H. van Raalte Marcel H. A. Muskiet Mark M. Smits Lennart Tonneijck Jaap A. Joles Bernt Johan von Scholten Emilie Hein Zobel Frederik Persson Trine Henriksen Lars Jorge Diaz Tine W. Hansen Henrik Enghusen Poulsen Peter Rossing
author_sort	Suvanjaa Sivalingam
title	The effect of liraglutide and sitagliptin on oxidative stress in persons with type 2 diabetes
title_short	The effect of liraglutide and sitagliptin on oxidative stress in persons with type 2 diabetes
title_full	The effect of liraglutide and sitagliptin on oxidative stress in persons with type 2 diabetes
title_fullStr	The effect of liraglutide and sitagliptin on oxidative stress in persons with type 2 diabetes
title_full_unstemmed	The effect of liraglutide and sitagliptin on oxidative stress in persons with type 2 diabetes
title_sort	effect of liraglutide and sitagliptin on oxidative stress in persons with type 2 diabetes
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/3bcc699d77684b339336dcb21eb97295
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The effect of liraglutide and sitagliptin on oxidative stress in persons with type 2 diabetes

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