title: TWO TREATMENT APPROACHES FOR HUMAN REGULAR U-500 INSULIN IN PATIENTS WITH TYPE 2 DIABETES NOT ACHIEVING ADEQUATE GLYCEMIC CONTROL ON HIGH-DOSE U-100 INSULIN THERAPY WITH OR WITHOUT ORAL AGENTS: A RANDOMIZED, TITRATION-TO-TARGET CLINICAL TRIAL.
abstract: To compare the efficacy and safety of 2 dosing regimens for human regular U-500 insulin (U-500R, 500 units/mL) replacing high-dose U-100 insulins with or without oral antihyperglycemic drugs in patients with inadequately controlled type 2 diabetes (T2D).
  
  
  
  We conducted a 24-week, open-label, parallel trial in 325 patients (demographics [means]: age, 55.4 years; diabetes duration, 15.2 years; body mass index, 41.9 kg/m(2); glycated hemoglobin [HbA1c], 8.7%; U-100 insulin dose, 287.5 units administered in 5 injections/day [median; range, 2 to 10]). Patients were randomized to thrice-daily (TID, n = 162) or twice-daily (BID, n = 163) U-500R after a 4-week lead-in period. The primary outcome was HbA1c change from baseline.
  
  
  
  After 24 weeks, both treatments demonstrated significant HbA1c reductions (TID, -1.12%; BID, -1.22%; both, P<.001) and clinical equivalence (difference, -0.10%; 95% confidence interval, -0.33 to 0.12%; noninferiority margin, 0.4%). Comparable increases in total daily U-500R dose (TID, 242.7 to 343.1 units; BID, 249.0 to 335.0 units) were observed. Incidence and rate of documented symptomatic hypoglycemia (≤70 mg/dL) were lower for TID versus BID (P = .003 and P = .02, respectively); severe hypoglycemia was similar between treatments. Weight gain was similar in both groups (TID, 5.4 kg; BID, 4.9 kg).
  
  
  
  Initiation and titration of U-500R using either algorithm (TID or BID) improves glycemic control effectively and safely with fewer injections in patients with T2D treated with high-dose/high-volume U-100 insulin. These results provide clinicians with a practical framework for using U-500R in severely insulin-resistant patients with suboptimally controlled T2D.
authors: Robert C
authors: RC
authors: Hood
authors: Richard F
authors: RF
authors: Arakaki
authors: Carol
authors: C
authors: Wysham
authors: Ying G
authors: YG
authors: Li
authors: Julie A
authors: JA
authors: Settles
authors: Jeffrey A
authors: JA
authors: Jackson
mesh_terms: D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000188:drug therapy*; D004334:Drug Administration Schedule; D005260:Female; D006442:Glycated Hemoglobin; D006801:Humans; D007003:Hypoglycemia / Q000097:blood / Q000188:drug therapy; D007333:Insulin Resistance; D061386:Insulin, Regular, Human / Q000008:administration & dosage* / Q000009:adverse effects / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D016896:Treatment Outcome
chemical_list: D006442:Glycated Hemoglobin; D061386:Insulin, Regular, Human; C517652:hemoglobin A1c protein, human