Exenatide treatment decreases fasting fibroblast growth factor 21 levels in patients with newly diagnosed type 2 diabetes mellitus

Aim. - Fibroblast growth factor 21 (FGF21) has been demonstrated to be a metabolic regulator with beneficial effects. Several studies have shown that type 2 diabetes mellitus (T2DM) patients have increased FGF21 levels and decreased expression of FGF receptors, suggesting a state of 'FGF21 resistance'. The aim of this study was to investigate the effects of the glucagon-like peptide (GLP)-1 receptor agonist exenatide on FGF21 levels and other metabolic parameters in patients with newly diagnosed T2DM. Methods. - A total of 100 participants, comprising 47 newly diagnosed T2DM patients and 53 age-matched healthy controls, were recruited. T2DM patients were assigned to 12 weeks of exenatide treatment. Their FGF21 levels and other metabolic parameters were measured before and after exenatide treatment. Results. - T2DM patients had significantly higher FGF21 levels than the controls. No difference in FGF21 was found between overweight and non-overweight control subgroups. In T2DM patients, exenatide treatment resulted in decreases in BMI, HbA(1c), total cholesterol and triglycerides, and also in FGF21 (149.17 +/- 81.36 vs 102.17 +/- 64.12 ng/mL; P < 0.01). Homoeostasis model assessment for insulin resistance (HOMA-IR) was also decreased [3.02 (2.10-4.63) vs 2.56 (1.80-4.13); P <0.05] while homoeostasis model assessment for beta-cell function (HOMA-B) was significantly higher after treatment [32.30 (17.82-59.42) vs 72.56 (46.63-99.58); P < 0.05]. The change in FGF21 (Delta FGF21) was negatively correlated with changes in fasting insulin (Delta insulin, r = -0.306; P < 0.05) and C-peptide (Delta C-peptide, r= -0.319; P < 0.05) levels. Conclusion. - Besides the improvement in insulin resistance and recovery of beta-cell function, 12 weeks of exenatide treatment may also play a role in lowering FGF21 levels in T2DM patients. (C) 2016 Elsevier Masson SAS. All rights reserved.