Effects of sodium-glucose cotransporter 2 inhibitor (dapagliflozin) on food intake and plasma fibroblast growth factor 21 levels in type 2 diabetes patients

The objective of this study was to investigate whether sodium-glucose cotransporter 2 inhibitors (SGLT2i) treatment in patients with type 2 diabetes induced compensatory hyperphagia by reducing fibroblast growth factor 21 (FGF21) secretion. This prospective study was performed in 26 type 2 diabetes patients treated with dapagliflozin (5 mg/day). Hormonal factors associated with glucose metabolism, dietary intakes estimated by brief self-administered diet-history questionnaire (BDHQ), body weight (BW), and body composition were measured at baseline, and 4 and 12 weeks after dapagliflozin. At 12 weeks, HbA1c levels and BW decreased significantly (both p < 0.0001). BMI at baseline was predictive to baseline log10 (FGF21) (p = 0.037). This study showed no change in FGF21, but insulin and glucagon levels decreased significantly (both p < 0.05). Although hyperphagia was found in 10 patients (38.5%), defining hyperphagia as >20% increase in carbohydrate intake, dapagliflozin treatment induced no hyperphagia, when analyzed by all subjects, and there was no significant association between changes in FGF21 levels and carbohydrate intake. On the other hand, a positive correlation between changes in FGF21 levels or carbohydrate intake and BW was observed (both p < 0.005). Taken together, this study demonstrates that the intervention to maintain the reduced levels in FGF21 is beneficial for BW reduction in type 2 diabetes patients treated with SGLT2i.