POSTPRANDIAL DYNAMICS OF PLASMA GLUCOSE, INSULIN, AND GLUCAGON IN PATIENTS WITH TYPE 2 DIABETES TREATED WITH SAXAGLIPTIN PLUS DAPAGLIFLOZIN ADD-ON TO METFORMIN THERAPY

Objective: To analyze changes in plasma glucose, insulin, and glucagon in relation to glycemic response during treatment with dual add-on of saxagliptin (SAXA) plus dapagliflozin (DAPA) to metformin XR (MET) compared with SAXA add-on or DAPA add-on alone to MET in patients with type 2 diabetes mellitus (T2DM) poorly controlled with MET. Methods: Double-blind trial in adults with glycated hemoglobin (HbA1c) >= 8.0 to >= 12.0% randomized to SAXA 5 mg/day plus DAPA 10 mg/day (n = 179), or SAXA 5 mg/day and placebo (n = 176), or DAPA 10 mg/day and placebo (n = 179) added to background MET >= 1,500 mg/day. The mean change from baseline in the area under the curve from 0 to 180 minutes (AUC(0-180) (min)) was calculated for glucose, insulin, and glucagon obtained during a liquid meal tolerance test (MTT). Results: Glucose AUC(0-180 min) was reduced more from baseline with SAXA + DAPA + MET (-12,940 mg/dL) compared with SAXA + MET (-6,309 mg/dL) and DAPA + MET (-11,247 mg/dL). Insulin AUC(0-180 min) significantly decreased with SAXA + DAPA + MET (-1,120 mu U/mL) and DAPA + MET (-1,019 mu U/mL) and increased with SAXA + MET (661 mu U/mL). Glucagon AUC(0-180 min) only increased with DAPA + MET (2,346 pg/mL). The changes in glucose (P<.0001) and insulin (P = .0003) AUC(0-180 min) correlated with change in HbA1c, whereas the change in glucagon AUC(0-180 min) did not (P = .27). Conclusions: When added to background MET, the combination of SAXA + DAPA provided additional reductions in glucose AUC(0-180 min) and HbA1c without the increase in insulin seen with SAXA and without the increase in glucagon seen with DAPA. Changes in insulin and glucose but not glucagon AUC(0-180 min) correlated with change in HbA1c.