High baseline FGF21 levels are associated with poor glucose-lowering efficacy of exenatide in patients with type 2 diabetes

Aims To investigate the association between fibroblast growth factor 21 (FGF21) levels and glycemic response to exenatide in patients with type 2 diabetes. Methods The exploratory analysis of a multi-center trial included 190 patients with type 2 diabetes inadequately controlled by monotherapy or combination therapy of metformin and insulin secretagogues. All participants received exenatide twice daily as an add-on therapy for 16 weeks. Serum FGF21 and other information at the baseline and end of follow-ups were obtained. Linear regression analysis was used to determine the correlations between baseline FGF21 levels and HbA1c reduction from baseline after the treatment. Results After 16 weeks of treatment with exenatide, a decline in the HbA1c levels from baseline was associated with higher baseline FGF21 levels among all participants ( r = 0.193, P = 0.008) and in subgroup of the participants receiving background metformin monotherapy ( r = 0.231, P = 0.034). Compared with patients in the lowest FGF21 quartile, patients in the highest FGF21 quartile showed a significantly weakened decline in HbA1c levels from baseline among all participants ( β = − 0.16 [95% Cl − 0.31 to − 0.01], P