title: Comparison of insulin lispro protamine suspension versus insulin glargine once daily added to oral antihyperglycaemic medications and exenatide in type 2 diabetes: a prospective randomized open-label trial.
abstract: OBJECTIVE
  To compare efficacy and safety of two, once-daily basal insulin formulations [insulin lispro protamine suspension (ILPS) vs. insulin glargine (glargine)] added to oral antihyperglycaemic medications (OAMs) and exenatide BID in suboptimally controlled type 2 diabetes (T2D) patients.
  
  
  METHODS
  This 24-week, open-label, multicentre trial randomized patients to bedtime ILPS (n = 171) or glargine (n = 168). Non-inferiority of ILPS versus glargine was assessed by comparing the upper limit of 95% confidence intervals (CIs) for change in haemoglobin A1c (HbA1c) from baseline to week 24 (adjusted for baseline HbA1c) with non-inferiority margin 0.4%.
  
  
  RESULTS
  Non-inferiority of ILPS versus glargine was demonstrated: least-squares mean between-treatment difference (ILPS minus glargine) (95% CI) was 0.22% (0.06, 0.38). Mean HbA1c reduction was less for ILPS- versus glargine-treated patients (-1.16 ± 0.84 vs. -1.40 ± 0.97%, p = 0.008). Endpoint HbA1c < 7.0% was achieved by 53.7% (ILPS) and 61.7% (glargine) (p = NS). Overall hypoglycaemia rates (p = NS) and severe hypoglycaemia incidence (p = NS) were similar. Nocturnal hypoglycaemia rate was higher in patients treated with ILPS versus glargine (p = 0.004). Weight gain was similar between groups (ILPS: 0.27 ± 3.38 kg; glargine: 0.66 ± 3.93 kg, p = NS). Endpoint total insulin doses were lower in patients treated with ILPS versus glargine (0.30 ± 0.17 vs. 0.37 ± 0.17 IU/kg/day, p < 0.001).
  
  
  CONCLUSIONS
  ILPS was non-inferior to glargine for HbA1c change over 24 weeks, but was associated with less HbA1c reduction and more nocturnal hypoglycaemia. Treat-to-target basal insulin therapy improves glycaemic control and is associated with minimal weight gain when added to OAMs and exenatide BID for suboptimally controlled T2D.
authors.affiliation: School of Medicine, University of Hawaii at Manoa, Honolulu, HI, USA.
authors.forename: R F
authors.initials: RF
authors.lastname: Arakaki
authors.forename: T C
authors.initials: TC
authors.lastname: Blevins
authors.forename: J K
authors.initials: JK
authors.lastname: Wise
authors.forename: D R
authors.initials: DR
authors.lastname: Liljenquist
authors.forename: H H
authors.initials: HH
authors.lastname: Jiang
authors.forename: J G
authors.initials: JG
authors.lastname: Jacobson
authors.forename: S A
authors.initials: SA
authors.lastname: Martin
authors.forename: J A
authors.initials: JA
authors.lastname: Jackson
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000368:Aged; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000378:metabolism; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D006943:Hyperglycemia / Q000188:drug therapy* / Q000378:metabolism; D007003:Hypoglycemia / Q000139:chemically induced; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D000069036:Insulin Glargine; D061268:Insulin Lispro / Q000008:administration & dosage* / Q000009:adverse effects; D049528:Insulin, Long-Acting / Q000008:administration & dosage* / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D011479:Protamines / Q000008:administration & dosage / Q000009:adverse effects; D016896:Treatment Outcome; D015430:Weight Gain; D055815:Young Adult
chemical_list: D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D000069036:Insulin Glargine; D061268:Insulin Lispro; D049528:Insulin, Long-Acting; D011479:Protamines; C517652:hemoglobin A1c protein, human
keywords: HbA1c; exenatide; glucagon-like peptide-1 receptor agonist therapy; glycaemic control; hypoglycaemia; insulin glargine; insulin lispro protamine suspension; type 2 diabetes