title: Patient-level meta-analysis of efficacy and hypoglycaemia in people with type 2 diabetes initiating insulin glargine 100U/mL or neutral protamine Hagedorn insulin analysed according to concomitant oral antidiabetes therapy.
abstract: OBJECTIVE
  Evaluate efficacy and hypoglycaemia according to concomitant oral antidiabetes drug (OAD) in people with type 2 diabetes initiating insulin glargine 100U/mL (Gla-100) or neutral protamine Hagedorn (NPH) insulin once daily.
  
  
  METHODS
  Four studies (target fasting plasma glucose [FPG] ⩽100mg/dL [⩽5.6mmol/L]; duration ⩾24weeks) were included. Standardised data from 2091 subjects (Gla-100, n=1024; NPH insulin, n=1067) were analysed. Endpoints included glycated haemoglobin (HbA1c) and FPG change, glycaemic target achievement, hypoglycaemia, weight change, and insulin dose.
  
  
  RESULTS
  Mean HbA1c and FPG reductions were similar with Gla-100 and NPH insulin regardless of concomitant OAD (P=0.184 and P=0.553, respectively) and similar proportions of subjects achieved HbA1c <7.0% (P=0.603). There was a trend for more subjects treated with Gla-100 achieving FPG ⩽100mg/dL versus NPH insulin (relative risk [RR] 1.09 [95% confidence interval (CI) 0.97-1.23]; P=0.135). Plasma glucose confirmed (<70mg/dL) overall and nocturnal hypoglycaemia incidences and rates were lower with Gla-100 versus NPH insulin (overall RR 0.93 [95% CI 0.87-1.00]; P=0.041; nocturnal RR 0.73 [95% CI 0.65-0.83]; P<0.001). After 24weeks, weight gain and insulin doses were higher with Gla-100 versus NPH insulin (2.7kg vs 2.3kg, P=0.009 and 0.42U/kg vs 0.39U/kg; P=0.003, respectively). Insulin doses were higher when either insulin was added to sulfonylurea alone.
  
  
  CONCLUSIONS
  Pooled results from treat-to-target trials in insulin-naïve people with type 2 diabetes demonstrate a significantly lower overall and nocturnal hypoglycaemia risk across different plasma glucose definitions with Gla-100 versus NPH insulin at similar glycaemic control. OAD therapy co-administered with Gla-100 or NPH insulin impacts glycaemic control and overall nocturnal hypoglycaemia risk.
authors.affiliation: Institute of Life Sciences, Swansea University, Swansea, UK. Electronic address: OwensDR@cardiff.ac.uk.
authors.forename: David R
authors.initials: DR
authors.lastname: Owens
authors.affiliation: Sanofi US, Inc., Bridgewater, NJ, USA.
authors.forename: Louise
authors.initials: L
authors.lastname: Traylor
authors.affiliation: Department of Statistics, University of Auckland, Auckland, New Zealand.
authors.forename: Peter
authors.initials: P
authors.lastname: Mullins
authors.affiliation: Sanofi, Frankfurt, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Landgraf
mesh_terms: D000284:Administration, Oral; D017326:Clinical Trials, Phase III as Topic / Q000706:statistics & numerical data; D017327:Clinical Trials, Phase IV as Topic / Q000706:statistics & numerical data; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy* / Q000453:epidemiology; D004359:Drug Therapy, Combination; D005260:Female; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D007003:Hypoglycemia / Q000139:chemically induced / Q000453:epidemiology*; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D015994:Incidence; D000069036:Insulin Glargine / Q000008:administration & dosage / Q000627:therapeutic use*; D007336:Insulin, Isophane / Q000627:therapeutic use*; D008297:Male; D016032:Randomized Controlled Trials as Topic / Q000706:statistics & numerical data; D013453:Sulfonylurea Compounds / Q000008:administration & dosage; D016896:Treatment Outcome; D015430:Weight Gain / Q000187:drug effects
chemical_list: D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D000069036:Insulin Glargine; D007336:Insulin, Isophane; D013453:Sulfonylurea Compounds
keywords: Glycaemic control; Hypoglycaemia; Insulin glargine; Metformin; Neutral protamine Hagedorn insulin; Sulfonylurea