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Effect of metformin on plasma metabolite profile in the Copenhagen Insulin and Metformin Therapy ( CIMT ) trial
Author(s) -
Safai N.,
Suvitaival T.,
Ali A.,
Spégel P.,
AlMajdoub M.,
Carstensen B.,
Vestergaard H.,
Ridderstråle M.
Publication year - 2018
Publication title -
diabetic medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.474
H-Index - 145
eISSN - 1464-5491
pISSN - 0742-3071
DOI - 10.1111/dme.13636
Subject(s) - metformin , medicine , valine , isoleucine , type 2 diabetes , placebo , endocrinology , leucine , metabolite , diabetes mellitus , carnitine , randomized controlled trial , insulin , pharmacology , amino acid , biochemistry , chemistry , alternative medicine , pathology
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 HbA 1c 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 ( LPE s), 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 1c ( P ‐interaction = 0.02 and 0.03, respectively). This association was not significant with HbA 1c 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 1c ‐lowering effect of metformin. Further studies of the association between metformin, carnitine and leucine/isoleucine are warranted.