Association of leptin and ghrelin changes with weight response after dapagliflozin treatment in type 2 diabetes: a prospective interventional study

Background: To compare changes in serum leptin and ghrelin according to weight response in patients with type 2 diabetes treated with dapagliflozin, a sodium-glucose cotransporter 2 inhibitor (SGLT2i).Methods: In this prospective single-arm interventional study, 97 patients received dapagliflozin 10 mg daily. Serum leptin and ghrelin were measured before treatment and after 3 months of dapagliflozin treatment. Participants were divided into two groups according to their 3-month glycated hemoglobin (HbA1c) level: the target group, with HbA1c ≤7.0% (n=45), and the above-target group, with HbA1c >7.0% (n=52). Additional analyses were performed according to body weight change: the weight-loss group (n=60) and the weight-gain group (n=37). Changes in serum leptin and ghrelin were compared between groups.Results: After 3 months of treatment, the mean HbA1c level was 6.7%±0.1% in the target group and 7.3%±0.2% in the above-target group. Serum leptin and ghrelin did not differ significantly between these groups. In the weight-loss group, serum leptin decreased significantly from 7.54±3.51 to 6.60±2.40 ng/mL (P<0.001), whereas in the weight-gain group, serum leptin increased significantly from 7.58±2.61 to 8.24±3.09 ng/mL (P<0.001). Serum ghrelin decreased significantly from 873.6±252.6 to 798.4±200.8 pg/mL in the weight-loss group (P=0.029), but did not change significantly in the weight-gain group, from 791.8±216.6 to 818.8±208.6 pg/mL (P=0.493).Conclusions: Reductions in serum leptin and ghrelin were associated with weight response after dapagliflozin treatment. Further studies are needed to identify strategies for addressing weight gain after SGLT2i treatment.