title: An analysis of early insulin glargine added to metformin with or without sulfonylurea: impact on glycaemic control and hypoglycaemia.
abstract: OBJECTIVE
  To evaluate the benefits of initiating insulin at an earlier versus later treatment stage, and regimens with/without sulfonylurea (SU).
  
  
  METHODS
  Pooled analysis of 11 prospective randomized clinical trials, including 2171 adults with uncontrolled type 2 diabetes initiating insulin glargine following a specific titration algorithm. Clinical outcomes were glycated haemoglobin A1c (HbA1c) reduction, per cent achieving HbA1c ≤ 7.0%, weight gain and hypoglycaemic events. Statistical analysis compared outcomes 24 weeks after basal insulin initiation in patients previously uncontrolled on 0/1 oral antidiabetic drug (OAD) versus 2 OADs, and in patients taking metformin (MET) or SU alone or in combination at baseline. A meta-analysis was also conducted.
  
  
  RESULTS
  For the pooled analysis, patients on 0/1 OAD and those on MET monotherapy at baseline had the largest 24-week reductions in HbA1c following the addition of insulin glargine (∼0.44 U/kg). Of patients failing MET/SU monotherapy and MET + SU in combination, 68.1, 50.4 and 56.4% achieved HbA1c ≤ 7.0%, respectively (p = 0.0006). Weight gain was lowest when basal insulin was added to MET. Patients on 0/1 OAD at baseline had significantly less symptomatic hypoglycaemia when basal insulin was added than those on 2 OADs (p = 0.0007). Despite higher insulin doses, those taking MET alone had less hypoglycaemia than those taking SU or MET + SU. Results were confirmed in the meta-analysis.
  
  
  CONCLUSIONS
  Adding insulin glargine to MET monotherapy early in treatment may provide efficacy/safety benefits over regimens including SU. This may reflect treatment earlier in the disease and supports the inclusion of insulin as a second step in the American Diabetes Association/European Association for the Study of Diabetes treatment algorithm.
authors.affiliation: Department of Endocrinology, Tulane University Medical Center, New Orleans, LA 70112, USA. vfonseca@tulane.edu
authors.forename: V
authors.initials: V
authors.lastname: Fonseca
authors.forename: J
authors.initials: J
authors.lastname: Gill
authors.forename: R
authors.initials: R
authors.lastname: Zhou
authors.forename: J
authors.initials: J
authors.lastname: Leahy
mesh_terms: D000465:Algorithms; D001786:Blood Glucose / Q000187:drug effects* / Q000502:physiology; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000503:physiopathology; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D006442:Glycated Hemoglobin / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D007003:Hypoglycemia / Q000188:drug therapy* / Q000503:physiopathology; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000494:pharmacology; D007328:Insulin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D000069036:Insulin Glargine; D049528:Insulin, Long-Acting; D008297:Male; D008687:Metformin / Q000008:administration & dosage* / Q000494:pharmacology; D008875:Middle Aged; D011446:Prospective Studies; D016032:Randomized Controlled Trials as Topic; D013453:Sulfonylurea Compounds / Q000008:administration & dosage* / Q000494:pharmacology; D016896:Treatment Outcome
chemical_list: D001786:Blood Glucose; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007328:Insulin; D000069036:Insulin Glargine; D049528:Insulin, Long-Acting; D008687:Metformin; D013453:Sulfonylurea Compounds