title: EFFECT OF TOTAL DAILY DOSE ON EFFICACY, DOSING, AND SAFETY OF 2 DOSE TITRATION REGIMENS OF HUMAN REGULAR U500 INSULIN IN SEVERELY INSULIN-RESISTANT PATIENTS WITH TYPE 2 DIABETES.
abstract: OBJECTIVE
  To examine the influence of baseline U-100 insulin total daily dose (TDD) on clinical outcomes in severely insulin-resistant patients with inadequately controlled type 2 diabetes treated with human regular U-500 insulin (U-500R) from the perspective of current dosing recommendations.
  
  
  METHODS
  Data from a recent prospective, randomized trial comparing thricedaily (TID) and twice-daily (BID) U-500R in 325 patients transitioned from high-dose/high-volume U-100 insulin were analyzed across baseline U-100 TDD units and units/kg subgroups (≤300 units [n = 224, 68.9%] and >300 units [n = 101, 31.1%]; ≤2 units/kg [n = 96, 29.5%] and >2 units/kg [n = 229, 70.5%]). Subgroup effects on treatment differences were evaluated, and outcomes between treatment-pooled subgroups were compared.
  
  
  RESULTS
  At 24 weeks, significant reductions in glycated hemoglobin (HbA1c) were observed for all subgroups (range: -1.01% to -1.38%, P<.05). Within-subgroup treatment effects were similar with no treatment-by-subgroup interactions; however, a greater reduction was noted in the >300 units subgroup (P = .04). No TID/BID differences within subgroups or treatment-by-subgroup interactions were observed for TDD or weight increase from baseline. Overall hypoglycemia rates were similar between treatments (within subgroups) and showed no interactions. However, rates were higher in the >300 units subgroup for severe hypoglycemia (P = .04) and in both higher-dose subgroups for documented symptomatic hypoglycemia ≤70 mg/dL (P<.001, units; P = .001, units/kg).
  
  
  CONCLUSIONS
  Both TID and BID U-500R were efficacious and safe across TDD subgroups, though higher hypoglycemia rates were observed in higher-dose, treatment-pooled subgroups. U-500R dosing recommendations have been updated accordingly.
  
  
  BACKGROUND
  AE = adverse event BID = twice daily HbA1c = glycated hemoglobin QID = 4 times daily RCT = randomized clinical trial T2D = type 2 diabetes TDD = total daily dose TID = thrice daily U-500R = human regular U-500 insulin.
authors.forename: Carol
authors.initials: C
authors.lastname: Wysham
authors.forename: Robert C
authors.initials: RC
authors.lastname: Hood
authors.forename: Mark L
authors.initials: ML
authors.lastname: Warren
authors.forename: Tao
authors.initials: T
authors.lastname: Wang
authors.forename: Tina M
authors.initials: TM
authors.lastname: Morwick
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Jackson