Changes in Levels of Biomarkers Associated with Adipocyte Function and Insulin and Glucagon Kinetics During Treatment with Dapagliflozin Among Obese Type 2 Diabetes Mellitus Patients

Abstract

Objectives: This study aimed to investigate changes in levels of biomarkers associated with adipocyte function and insulin and glucagon kinetics after a meal tolerance test (MTT) during treatment with dapagliflozin among obese type 2 diabetes mellitus (T2DM) patients. Methods: T2DM patients with hemoglobin A1c (HbA1c) levels >6.5 % and body mass index (BMI) >25 kg/m2 were treated with dapagliflozin 5 mg/day for at least 12 weeks. HbA1c, body weight, ketone bodies, adiponectin, plasminogen activator inhibitor-1 (PAI-1), and C-reactive protein (CRP) were measured before and after treatment with dapagliflozin. A subset of patients underwent an MTT. Results: Of 27 participating patients (mean age 47.9 years; 17 males), five were drug-naive and 22 were treated with other antidiabetic agents, including insulin and glucagon-like peptide-1 (GLP-1) receptor agonists. Following treatment with dapagliflozin, HbA1c levels significantly improved (7.44 ± 0.56 to 6.70 ± 0.0.57 %; p < 0.01), body weight significantly decreased (90.9 ± 16.5 to 87.1 ± 15.9 kg; p < 0.01), ketone bodies increased, adiponectin significantly increased, and high-sensitivity CRP tended to decrease. During the MTT, blood glucose ΔAUC2 significantly decreased, glucagon ΔAUC2 increased, and immunoreactive insulin (IRI) did not change in 11 of 27 patients. Conclusion: Although ketone bodies increased significantly, adiponectin increased and high-sensivity CRP decreased significantly. These findings suggest that sodium-glucose cotransporter-2 (SGLT2) inhibitors may potentially improve adipocyte function in treating obese T2DM patients.