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

Safai, N.; Suvitaival, T.; Ali, A.; Spégel, P. LU ; Al-Majdoub, M. LU ; Carstensen, B.; Vestergaard, H. and Ridderstråle, M. LU (2018) In Diabetic Medicine
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 (CIMT) 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... (More)

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 (CIMT) 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.

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author
organization
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type
Contribution to journal
publication status
epub
subject
in
Diabetic Medicine
publisher
Wiley-Blackwell
external identifiers
  • scopus:85046422867
ISSN
0742-3071
DOI
10.1111/dme.13636
language
English
LU publication?
yes
id
3ff6813d-6838-4218-88ba-73a460a0a912
date added to LUP
2018-05-17 14:26:44
date last changed
2018-05-29 11:55:13
@article{3ff6813d-6838-4218-88ba-73a460a0a912,
  abstract     = {<p>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 HbA<sub>1c</sub> outcome. Methods: Post hoc analysis of the Copenhagen Insulin and Metformin Therapy (CIMT) 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 HbA<sub>1c</sub> (P-interaction = 0.02 and 0.03, respectively). This association was not significant with HbA<sub>1c</sub> 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 HbA<sub>1c</sub>-lowering effect of metformin. Further studies of the association between metformin, carnitine and leucine/isoleucine are warranted.</p>},
  author       = {Safai, N. and Suvitaival, T. and Ali, A. and Spégel, P. and Al-Majdoub, M. and Carstensen, B. and Vestergaard, H. and Ridderstråle, M.},
  issn         = {0742-3071},
  language     = {eng},
  month        = {01},
  publisher    = {Wiley-Blackwell},
  series       = {Diabetic Medicine},
  title        = {Effect of metformin on plasma metabolite profile in the Copenhagen Insulin and Metformin Therapy (CIMT) trial},
  url          = {http://dx.doi.org/10.1111/dme.13636},
  year         = {2018},
}