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Impact of metformin versus repaglinide on non-glycaemic cardiovascular risk markers related to inflammation and endothelial dysfunction in non-obese patients with type 2 diabetes

Lund, Soren S; Tarnow, Lisc; Stehouwer, Coen D A; Schalkwijk, Casper G; Teerlink, Tom; Gram, Jorgen; Winther, Kaj; Frandsen, Merete; Smidt, Ulla M and Pedersen, Oluf, et al. (2008) In European Journal of Endocrinology 158(5). p.631-641
Abstract
Objective: In patients with type 2 diabetes mellitus (T2DM), biomarkers reflecting inflammation and endothelial dysfunction have been linked to cardiovascular disease (CVD biomarkers) and metabolic regulation. In T2DM patients, metformin and insulin secretagogues have demonstrated equal anti-hyperglycaemic potency. Here, we report the effect of metformin versus an insulin secretagogue, repaglinide, on CVD biomarkers in non-obese T2DM patients. Design and methods: Single-centre, double-masked, double-dummy, crossover study during 2x4 months involving 96 non-obese (body mass index <= 27kg/m(2)) insulin-naive T2DM patients. At enrolment, previous oral hypoglycaemic agents were stopped and the patients entered a 1-month run- on diet-only... (More)
Objective: In patients with type 2 diabetes mellitus (T2DM), biomarkers reflecting inflammation and endothelial dysfunction have been linked to cardiovascular disease (CVD biomarkers) and metabolic regulation. In T2DM patients, metformin and insulin secretagogues have demonstrated equal anti-hyperglycaemic potency. Here, we report the effect of metformin versus an insulin secretagogue, repaglinide, on CVD biomarkers in non-obese T2DM patients. Design and methods: Single-centre, double-masked, double-dummy, crossover study during 2x4 months involving 96 non-obese (body mass index <= 27kg/m(2)) insulin-naive T2DM patients. At enrolment, previous oral hypoglycaemic agents were stopped and the patients entered a 1-month run- on diet-only treatment. Hereafter, patients were randomized to either 2 mg repaglinide thrice daily followed by 1 g metformin twice daily or vice versa each during 4 months with a 1-month washout between interventions. Results: Levels of tumour necrosis factor-alpha, plasminogen activator inhibitor-1 antigen, tissue-type plasminogen activator antigen, von Willebrand factor, soluble intercellular adhesion molecule-1 and soluble E-selectin were significantly lower during metformin versus repaglinide treatments. In contrast, Amadori albumin and heart rate were higher during metformin versus repaglinide. Levels of interleukin-6. fibrinogen, soluble vascular cell adhesion molecule-1, asymmetric dimethylarginine and advanced glycation end products as well as glycaemic levels (previously reported) and 24-h blood pressure were similar between treatments. Adjustment for known macrovascular disease did not affect the between-treatment: effects. Conclusions: In non-obese T2DM patients, metformin was more effective in reducing selected biomarkers reflecting inflammation and endothelial dysfunction compared with repaglinide despite similar glycaemic levels between treatments. (Less)
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type
Contribution to journal
publication status
published
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European Journal of Endocrinology
volume
158
issue
5
pages
631 - 641
publisher
Society of the European Journal of Endocrinology
external identifiers
  • wos:000255789200006
  • scopus:43149110575
ISSN
1479-683X
DOI
10.1530/EJE-07-0815
language
English
LU publication?
yes
id
1eeb8122-3209-41f1-bded-5b17b0eb1111 (old id 1204204)
date added to LUP
2008-09-17 12:16:54
date last changed
2017-09-03 03:35:57
@article{1eeb8122-3209-41f1-bded-5b17b0eb1111,
  abstract     = {Objective: In patients with type 2 diabetes mellitus (T2DM), biomarkers reflecting inflammation and endothelial dysfunction have been linked to cardiovascular disease (CVD biomarkers) and metabolic regulation. In T2DM patients, metformin and insulin secretagogues have demonstrated equal anti-hyperglycaemic potency. Here, we report the effect of metformin versus an insulin secretagogue, repaglinide, on CVD biomarkers in non-obese T2DM patients. Design and methods: Single-centre, double-masked, double-dummy, crossover study during 2x4 months involving 96 non-obese (body mass index &lt;= 27kg/m(2)) insulin-naive T2DM patients. At enrolment, previous oral hypoglycaemic agents were stopped and the patients entered a 1-month run- on diet-only treatment. Hereafter, patients were randomized to either 2 mg repaglinide thrice daily followed by 1 g metformin twice daily or vice versa each during 4 months with a 1-month washout between interventions. Results: Levels of tumour necrosis factor-alpha, plasminogen activator inhibitor-1 antigen, tissue-type plasminogen activator antigen, von Willebrand factor, soluble intercellular adhesion molecule-1 and soluble E-selectin were significantly lower during metformin versus repaglinide treatments. In contrast, Amadori albumin and heart rate were higher during metformin versus repaglinide. Levels of interleukin-6. fibrinogen, soluble vascular cell adhesion molecule-1, asymmetric dimethylarginine and advanced glycation end products as well as glycaemic levels (previously reported) and 24-h blood pressure were similar between treatments. Adjustment for known macrovascular disease did not affect the between-treatment: effects. Conclusions: In non-obese T2DM patients, metformin was more effective in reducing selected biomarkers reflecting inflammation and endothelial dysfunction compared with repaglinide despite similar glycaemic levels between treatments.},
  author       = {Lund, Soren S and Tarnow, Lisc and Stehouwer, Coen D A and Schalkwijk, Casper G and Teerlink, Tom and Gram, Jorgen and Winther, Kaj and Frandsen, Merete and Smidt, Ulla M and Pedersen, Oluf and Parving, Hans-Henrik and Vaag, Allan},
  issn         = {1479-683X},
  language     = {eng},
  number       = {5},
  pages        = {631--641},
  publisher    = {Society of the European Journal of Endocrinology},
  series       = {European Journal of Endocrinology},
  title        = {Impact of metformin versus repaglinide on non-glycaemic cardiovascular risk markers related to inflammation and endothelial dysfunction in non-obese patients with type 2 diabetes},
  url          = {http://dx.doi.org/10.1530/EJE-07-0815},
  volume       = {158},
  year         = {2008},
}