title: Reduced risk of hypoglycemia with once-daily glargine versus twice-daily NPH and number needed to harm with NPH to demonstrate the risk of one additional hypoglycemic event in type 2 diabetes: Evidence from a long-term controlled trial.
abstract: OBJECTIVE
  This analysis evaluated HbA1c-adjusted hypoglycemia risk with glargine versus neutral protamine Hagedorn (NPH) over a 5-year study in patients with Type 2 diabetes mellitus (T2DM). Clinical significance was assessed using number needed to harm (NNH) to demonstrate the risk of one additional patient experiencing at least one hypoglycemic event.
  
  
  METHODS
  Individual patient-level data for symptomatic documented hypoglycemia and HbA1c values from a 5-year randomized study comparing once-daily glargine (n=513) with twice-daily NPH (n=504) were analyzed. Symptomatic hypoglycemia was categorized according to concurrent self-monitoring blood glucose levels and need for assistance. Hypoglycemic events per patient-year as a function of HbA1c were fitted by negative binomial regression using treatment and HbA1c at endpoint as independent variables. An estimate of NNH was derived from logistic regression models.
  
  
  RESULTS
  The cumulative number of symptomatic hypoglycemia events was consistently lower with glargine compared with NPH over 5years. Compared with twice-daily NPH, once-daily glargine treatment resulted in significantly lower adjusted odds ratios (OR) for all daytime hypoglycemia (OR 0.74; p=0.030) and any severe event (OR 0.64; p=0.035), representing a 26% and 36% reduction in the odds of daytime and severe hypoglycemia, respectively. Our model predicts that, if 25 patients were treated with NPH instead of glargine, then one additional patient would experience at least one severe hypoglycemic event.
  
  
  CONCLUSIONS
  This analysis of long-term insulin treatment confirms findings from short-term studies and demonstrates that glargine provides sustained, clinically meaningful reductions in risk of hypoglycemia compared with NPH in patients with T2DM.
authors.affiliation: Dallas Diabetes and Endocrine Center at Medical City, Dallas, TX, USA. Electronic address: juliorosenstock@dallasdiabetes.com.
authors.forename: Julio
authors.initials: J
authors.lastname: Rosenstock
authors.affiliation: Tulane University Health Sciences Center, New Orleans, LA, USA.
authors.forename: Vivian
authors.initials: V
authors.lastname: Fonseca
authors.affiliation: Sanofi Deutschland GmbH, Frankfurt, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Schinzel
authors.affiliation: Sanofi, Paris, France.
authors.forename: Marie-Paule
authors.initials: MP
authors.lastname: Dain
authors.affiliation: Department of Statistics, University of Auckland, Auckland, New Zealand.
authors.forename: Peter
authors.initials: P
authors.lastname: Mullins
authors.affiliation: Oregon Health & Science University, Portland, OR, USA.
authors.forename: Matthew
authors.initials: M
authors.lastname: Riddle
mesh_terms: D000328:Adult; D000368:Aged; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007003:Hypoglycemia / Q000139:chemically induced* / Q000453:epidemiology; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D000069036:Insulin Glargine; D007336:Insulin, Isophane / Q000008:administration & dosage* / Q000009:adverse effects*; D049528:Insulin, Long-Acting / Q000008:administration & dosage* / Q000009:adverse effects; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D012306:Risk; D040242:Risk Reduction Behavior; D013997:Time Factors
chemical_list: D007004:Hypoglycemic Agents; D049528:Insulin, Long-Acting; D000069036:Insulin Glargine; D007336:Insulin, Isophane
keywords: Clinical diabetes; Clinical science and care; Glargine; Hypoglycemia; NPH