title: How much is too much? Outcomes in patients using high-dose insulin glargine.
abstract: OBJECTIVE
  Many patients with type 2 diabetes mellitus (T2DM) do not achieve glycaemic control targets on basal insulin regimens. This analysis investigated characteristics, clinical outcomes and impact of concomitant oral antidiabetes drugs (OADs) in patients with T2DM treated with high-dose insulin glargine.
  
  
  METHODS
  Patient-level data were pooled from 15 randomised, treat-to-target trials in patients with T2DM treated with insulin glargine ± OADs for ≥ 24 weeks. Data were stratified according to whether patients exceeded three insulin dose cut-off levels (> 0.5, > 0.7 and > 1.0 IU/kg). End-points included glycated haemoglobin A1c (A1C), fasting plasma glucose, body weight, and overall, nocturnal and severe hypoglycaemia.
  
  
  RESULTS
  Data from 2837 insulin-naïve patients were analysed. Patients with insulin titrated beyond the three doses investigated had significantly higher baseline A1C levels and were younger, with shorter diabetes duration than those at/below cut-offs (p < 0.05 for all cut-offs); they also had greater weight gain (p < 0.001 for the > 0.5 and > 0.7 IU/kg cut-offs) than those who did not exceed the cut-offs, regardless of concomitant OAD. Patients on concomitant metformin alone had higher insulin doses at Week 24, but achieved greater reductions in A1C, less weight gain and lower hypoglycaemia rates than patients on a concomitant sulfonylurea or metformin plus a sulfonylurea, regardless of whether cut-offs were exceeded.
  
  
  CONCLUSIONS
  In patients with T2DM, increasing basal insulin doses above 0.5 IU/kg may not improve glycaemic control; treatment strategies targeting postprandial glucose control should be considered for such patients.
authors.affiliation: Mercy Diabetes Center, Janesville, WI, USA.
authors.forename: T
authors.initials: T
authors.lastname: Reid
authors.affiliation: Analysta Inc., Somerset, NJ, USA.
authors.forename: L
authors.initials: L
authors.lastname: Gao
authors.affiliation: Sanofi US, Inc., Bridgewater, NJ, USA.
authors.forename: J
authors.initials: J
authors.lastname: Gill
authors.affiliation: Sanofi US, Inc., Bridgewater, NJ, USA.
authors.forename: A
authors.initials: A
authors.lastname: Stuhr
authors.affiliation: Sanofi US, Inc., Bridgewater, NJ, USA.
authors.forename: L
authors.initials: L
authors.lastname: Traylor
authors.affiliation: Sanofi US, Inc., Bridgewater, NJ, USA.
authors.forename: A
authors.initials: A
authors.lastname: Vlajnic
authors.affiliation: Johnstone Memorial Diabetes Care Center, Abingdon, VA, USA.
authors.forename: A
authors.initials: A
authors.lastname: Rhinehart
mesh_terms: D000328:Adult; D000368:Aged; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy*; D004359:Drug Therapy, Combination / Q000009:adverse effects; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007003:Hypoglycemia / Q000139:chemically induced; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D000069036:Insulin Glargine / Q000008:administration & dosage* / Q000009:adverse effects; D008297:Male; D008687:Metformin / Q000627:therapeutic use; D008875:Middle Aged; D013453:Sulfonylurea Compounds / Q000627:therapeutic use; D015430:Weight Gain / Q000187:drug effects
chemical_list: D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D000069036:Insulin Glargine; D008687:Metformin; D013453:Sulfonylurea Compounds; C517652:hemoglobin A1c protein, human