title: Modulation of insulin dose titration using a hypoglycaemia-sensitive algorithm: insulin glargine versus neutral protamine Hagedorn insulin in insulin-naïve people with type 2 diabetes.
abstract: OBJECTIVE
  To examine whether insulin glargine can lead to better control of glycated haemoglobin (HbA1c) than that achieved by neutral protamine Hagedorn (NPH) insulin, using a protocol designed to limit nocturnal hypoglycaemia.
  
  
  METHODS
  The present study, the Least One Oral Antidiabetic Drug Treatment (LANCELOT) Study, was a 36-week, randomized, open-label, parallel-arm study conducted in Europe, Asia, the Middle East and South America. Participants were randomized (1:1) to begin glargine or NPH, on background of metformin with glimepiride. Weekly insulin titration aimed to achieve median prebreakfast and nocturnal plasma glucose levels ≤5.5 mmol/l, while limiting values ≤4.4 mmol/l.
  
  
  RESULTS
  The efficacy population (n = 701) had a mean age of 57 years, a mean body mass index of 29.8 kg/m², a mean duration of diabetes of 9.2 years and a mean HbA1c level of 8.2% (66 mmol/mol). At treatment end, HbA1c values and the proportion of participants with HbA1c <7.0 % (<53 mmol/mol) were not significantly different for glargine [7.1 % (54 mmol/mol) and 50.3%] versus NPH [7.2 % (55 mmol/mol) and 44.3%]. The rate of symptomatic nocturnal hypoglycaemia, confirmed by plasma glucose ≤3.9 or ≤3.1 mmol/l, was 29 and 48% less with glargine than with NPH insulin. Other outcomes were similar between the groups.
  
  
  CONCLUSIONS
  Insulin glargine was not superior to NPH insulin in improving glycaemic control. The insulin dosing algorithm was not sufficient to equalize nocturnal hypoglycaemia between the two insulins. This study confirms, in a globally heterogeneous population, the reduction achieved in nocturnal hypoglycaemia while attaining good glycaemic control with insulin glargine compared with NPH, even when titrating basal insulin to prevent nocturnal hypoglycaemia rather than treating according to normal fasting glucose levels.
authors: Institute for Cellular Medicine - Diabetes, Newcastle University, Newcastle upon Tyne, UK.
authors: P D
authors: PD
authors: Home
authors: G B
authors: GB
authors: Bolli
authors: C
authors: C
authors: Mathieu
authors: C
authors: C
authors: Deerochanawong
authors: W
authors: W
authors: Landgraf
authors: C
authors: C
authors: Candelas
authors: V
authors: V
authors: Pilorget
authors: M-P
authors: MP
authors: Dain
authors: M C
authors: MC
authors: Riddle
mesh_terms: D000368:Aged; D001208:Asia; D015190:Blood Glucose Self-Monitoring; D002940:Circadian Rhythm; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy*; D054796:Drug Dosage Calculations; D004351:Drug Resistance; D004359:Drug Therapy, Combination / Q000009:adverse effects; D005060:Europe; D005260:Female; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D006943:Hyperglycemia / Q000517:prevention & control*; D007003:Hypoglycemia / Q000139:chemically induced / Q000517:prevention & control*; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D000069036:Insulin Glargine; D007336:Insulin, Isophane / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D049528:Insulin, Long-Acting / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D008297:Male; D008687:Metformin / Q000627:therapeutic use; D008875:Middle Aged; D008877:Middle East; D013019:South Africa; D013453:Sulfonylurea Compounds / Q000627:therapeutic use
chemical_list: D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D000069036:Insulin Glargine; D007336:Insulin, Isophane; D049528:Insulin, Long-Acting; D008687:Metformin; D013453:Sulfonylurea Compounds; C517652:hemoglobin A1c protein, human; C057619:glimepiride
keywords: NPH insulin; hypoglycaemia-sensitive algorithm; insulin glargine