title: Postprandial dynamics of plasma glucose, insulin, and glucagon in patients with type 2 diabetes treated with saxagliptin plus dapagliflozin add-on to metformin therapy.
abstract: 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 (AUC0-180 min) was calculated for glucose, insulin, and glucagon obtained during a liquid meal tolerance test (MTT).
  
  
  RESULTS
  Glucose AUC0-180 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 AUC0-180 min significantly decreased with SAXA + DAPA + MET (-1,120 μU/mL) and DAPA + MET (-1,019 μU/mL) and increased with SAXA + MET (661 μU/mL). Glucagon AUC0-180 min only increased with DAPA + MET (2,346 pg/mL). The changes in glucose (P<.0001) and insulin (P = .0003) AUC0-180 min correlated with change in HbA1c, whereas the change in glucagon AUC0-180 min did not (P = .27).
  
  
  CONCLUSIONS
  When added to background MET, the combination of SAXA + DAPA provided additional reductions in glucose AUC0-180 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 AUC0-180 min correlated with change in HbA1c.
authors.affiliation: Bristol-Myers Squibb, Princeton, New Jersey.
authors.forename: Lars
authors.initials: L
authors.lastname: Hansen
authors.affiliation: Bristol-Myers Squibb, Princeton, New Jersey.
authors.forename: Nayyar
authors.initials: N
authors.lastname: Iqbal
authors.affiliation: AstraZeneca, Mölndal, Sweden.
authors.forename: Ella
authors.initials: E
authors.lastname: Ekholm
authors.affiliation: AstraZeneca, Wilmington, Delaware.
authors.forename: William
authors.initials: W
authors.lastname: Cook
authors.affiliation: AstraZeneca, Wilmington, Delaware.
authors.forename: Boaz
authors.initials: B
authors.lastname: Hirshberg