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±64.12ng/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 β-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 (ΔFGF21) was negatively correlated with changes in fasting insulin (Δinsulin, r=-0.306; P<0.05) and C-peptide (ΔC-peptide, r=-0.319; P<0.05) levels.

Conclusion: Besides the improvement in insulin resistance and recovery of β-cell function, 12 weeks of exenatide treatment may also play a role in lowering FGF21 levels in T2DM patients.