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Effect of metformin on plasma metabolite profile in the Copenhagen Insulin and Metformin Therapy (CIMT) trial

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@article{d2bb86c9cddd4367bb7f8a4fa00acea3,
title = "Effect of metformin on plasma metabolite profile in the Copenhagen Insulin and Metformin Therapy (CIMT) trial",
abstract = "AIM: Metformin is the first-line treatment for Type 2 diabetes. However, not all people benefit from this drug. Our aim was to investigate the effects of metformin on the plasma metabolome and whether the pretreatment metabolite profile can predict HbA1c outcome.METHODS: Post hoc analysis of the Copenhagen Insulin and Metformin Therapy (CMIT) trial, a multicentre study from May 2008 to December 2012, was carried out. We used a non-target method to analyse 87 plasma metabolites in participants with Type 2 diabetes (n = 370) who were randomized in a 1 : 1 ratio to 18 months of metformin or placebo treatment. Metabolites were measured by liquid chromatography-mass spectrometry at baseline and at 18-month follow-up and the data were analysed using a linear mixed-effect model.RESULTS: At baseline, participants who were on metformin before the trial (n = 312) had higher levels of leucine/isoleucine and five lysophosphatidylethanolamines (LPEs), and lower levels of carnitine and valine compared with metformin-na{\"i}ve participants (n = 58). At follow-up, participants randomized to metformin (n = 188) had elevated levels of leucine/isoleucine and reduced carnitine, tyrosine and valine compared with placebo (n = 182). At baseline, participants on metformin treatment with the highest levels of carnitine C10:1 and leucine/isoleucine had the lowest HbA1c (P-interaction = 0.02 and 0.03, respectively). This association was not significant with HbA1c at follow-up.CONCLUSIONS: Metformin treatment is associated with decreased levels of valine, tyrosine and carnitine, and increased levels of leucine/isoleucine. None of the identified metabolites can predict the HbA1c -lowering effect of metformin. Further studies of the association between metformin, carnitine and leucine/isoleucine are warranted. This article is protected by copyright. All rights reserved.",
keywords = "Journal Article",
author = "N Safai and T Suvitaival and Ali A and P Sp{\'e}gel and M Al-Majdoub and B Carstensen and H Vestergaard and M Ridderstr{\aa}le and {CIMT Trial Group} and Louise Lundby-Christensen and Lise Tarnow and Birger Thorsteinsson and Christian Gluud and R{\o}der, {Michael Einar} and Niels Wiinberg",
note = "This article is protected by copyright. All rights reserved.",
year = "2018",
month = jul,
doi = "10.1111/dme.13636",
language = "English",
volume = "35",
pages = "944--953",
journal = "Diabetic Medicine",
issn = "1464-5491",
publisher = "Wiley-Blackwell Publishing Ltd",
number = "7",

}

RIS

TY - JOUR

T1 - Effect of metformin on plasma metabolite profile in the Copenhagen Insulin and Metformin Therapy (CIMT) trial

AU - Safai, N

AU - Suvitaival, T

AU - A, Ali

AU - Spégel, P

AU - Al-Majdoub, M

AU - Carstensen, B

AU - Vestergaard, H

AU - Ridderstråle, M

AU - CIMT Trial Group

AU - Røder, Michael Einar

AU - Wiinberg, Niels

A2 - Lundby-Christensen, Louise

A2 - Tarnow, Lise

A2 - Thorsteinsson, Birger

A2 - Gluud, Christian

N1 - This article is protected by copyright. All rights reserved.

PY - 2018/7

Y1 - 2018/7

N2 - AIM: Metformin is the first-line treatment for Type 2 diabetes. However, not all people benefit from this drug. Our aim was to investigate the effects of metformin on the plasma metabolome and whether the pretreatment metabolite profile can predict HbA1c outcome.METHODS: Post hoc analysis of the Copenhagen Insulin and Metformin Therapy (CMIT) trial, a multicentre study from May 2008 to December 2012, was carried out. We used a non-target method to analyse 87 plasma metabolites in participants with Type 2 diabetes (n = 370) who were randomized in a 1 : 1 ratio to 18 months of metformin or placebo treatment. Metabolites were measured by liquid chromatography-mass spectrometry at baseline and at 18-month follow-up and the data were analysed using a linear mixed-effect model.RESULTS: At baseline, participants who were on metformin before the trial (n = 312) had higher levels of leucine/isoleucine and five lysophosphatidylethanolamines (LPEs), and lower levels of carnitine and valine compared with metformin-naïve participants (n = 58). At follow-up, participants randomized to metformin (n = 188) had elevated levels of leucine/isoleucine and reduced carnitine, tyrosine and valine compared with placebo (n = 182). At baseline, participants on metformin treatment with the highest levels of carnitine C10:1 and leucine/isoleucine had the lowest HbA1c (P-interaction = 0.02 and 0.03, respectively). This association was not significant with HbA1c at follow-up.CONCLUSIONS: Metformin treatment is associated with decreased levels of valine, tyrosine and carnitine, and increased levels of leucine/isoleucine. None of the identified metabolites can predict the HbA1c -lowering effect of metformin. Further studies of the association between metformin, carnitine and leucine/isoleucine are warranted. This article is protected by copyright. All rights reserved.

AB - AIM: Metformin is the first-line treatment for Type 2 diabetes. However, not all people benefit from this drug. Our aim was to investigate the effects of metformin on the plasma metabolome and whether the pretreatment metabolite profile can predict HbA1c outcome.METHODS: Post hoc analysis of the Copenhagen Insulin and Metformin Therapy (CMIT) trial, a multicentre study from May 2008 to December 2012, was carried out. We used a non-target method to analyse 87 plasma metabolites in participants with Type 2 diabetes (n = 370) who were randomized in a 1 : 1 ratio to 18 months of metformin or placebo treatment. Metabolites were measured by liquid chromatography-mass spectrometry at baseline and at 18-month follow-up and the data were analysed using a linear mixed-effect model.RESULTS: At baseline, participants who were on metformin before the trial (n = 312) had higher levels of leucine/isoleucine and five lysophosphatidylethanolamines (LPEs), and lower levels of carnitine and valine compared with metformin-naïve participants (n = 58). At follow-up, participants randomized to metformin (n = 188) had elevated levels of leucine/isoleucine and reduced carnitine, tyrosine and valine compared with placebo (n = 182). At baseline, participants on metformin treatment with the highest levels of carnitine C10:1 and leucine/isoleucine had the lowest HbA1c (P-interaction = 0.02 and 0.03, respectively). This association was not significant with HbA1c at follow-up.CONCLUSIONS: Metformin treatment is associated with decreased levels of valine, tyrosine and carnitine, and increased levels of leucine/isoleucine. None of the identified metabolites can predict the HbA1c -lowering effect of metformin. Further studies of the association between metformin, carnitine and leucine/isoleucine are warranted. This article is protected by copyright. All rights reserved.

KW - Journal Article

U2 - 10.1111/dme.13636

DO - 10.1111/dme.13636

M3 - Journal article

C2 - 29633349

VL - 35

SP - 944

EP - 953

JO - Diabetic Medicine

JF - Diabetic Medicine

SN - 1464-5491

IS - 7

ER -

ID: 53618303