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

Søren S. Lund*, Lise Tarnow, Coen D.A. Stehouwer, Casper G. Schalkwijk, Tom Teerlink, Jørgen Gram, Kaj Winther, Merete Frandsen, Ulla M. Smidt, Oluf Pedersen, Hans Henrik Parving, Allan A. Vaag

*Corresponding author af dette arbejde

    Publikation: Bidrag til tidsskriftArtikelForskningpeer review

    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 2 × 4 months involving 96 non-obese (body mass index ≤27 kg/m2) insulin-naïve T2DM patients. At enrolment, previous oral hypoglycaemic agents were stopped and the patients entered a 1-month runnin 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-α, 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 interteukin-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.

    OriginalsprogEngelsk
    Sider (fra-til)631-641
    Antal sider11
    TidsskriftEuropean Journal of Endocrinology
    Vol/bind158
    Udgave nummer5
    DOI
    StatusUdgivet - 1 maj 2008

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