title: Efficacy and risk of hypoglycemia with use of insulin glargine or comparators in patients with cardiovascular risk factors.
abstract: BACKGROUND
  Cardiovascular risk factors (CVRFs) may complicate optimization of therapy in patients with type 2 diabetes mellitus (T2DM) inadequately controlled with oral antidiabetes drugs (OADs). We assessed the influence of patient baseline CVRFs on efficacy and rate of hypoglycemia with use of insulin glargine (glargine) added to ongoing OAD treatment compared with alternative therapeutic options; namely, intensification of lifestyle interventions or adding OADs, neutral protamine Hagedorn (NPH), lispro, or premixed insulin in patients failing OADs.
  
  
  METHODS
  Patient-level data were pooled from 9 randomized controlled trials of glargine and comparators for 24 weeks in insulin-naive patients with T2DM inadequately controlled on OADs. Efficacy (goal attainment-glycated hemoglobin (HbA1c) level ≤ 7.0% or decrease ≥ 1.0% change from baseline) and hypoglycemia rates (symptomatic, confirmed, nocturnal, or severe) were compared for patients treated with glargine (n = 1462) and pooled (n = 1476) and individual comparators, overall; and in patients with hypertension (~69%), dyslipidemia (~58%), history of cardiovascular disease (~25%), or any CVRF (~83%) at baseline.
  
  
  RESULTS
  The patient groups were well-balanced at baseline (HbA1c level 8.7%; diabetes duration, 8.6 years). Use of glargine was associated with greater patient goal attainment (57.7% vs 51.4% for HbA1c level ≤ 7.0%; P < 0.001), modestly larger reductions in HbA1c level (-1.68% vs -1.51%; P < 0.001), and less symptomatic hypoglycemia than occurred with pooled comparators, regardless of patient CVRFs (5.04 vs 7.01 events/patient-year of exposure, respectively; P < 0.001). Reductions in HbA1c level and hypoglycemia rates were significantly greater with glargine use than with intensification of OADs or lifestyle modifications, overall, and in patients with any CVRF. Reductions in HbA1c level were greater and hypoglycemia rates lower with use of glargine compared with premixed insulin, overall, and in patients with any CVRF. Reductions in HbA1c level were similar and hypoglycemia rates lower with use of glargine, NPH, and lispro insulin, regardless of patient CVRFs.
  
  
  CONCLUSIONS
  The glycemic benefits of glargine use compared with alternative therapeutic options are maintained without excess hypoglycemia in patients with CVRFs.
authors.affiliation: Director, Ochsner Diabetes Clinical Research Unit, Department of Endocrinology, Ochsner Medical Center, New Orleans, LA. lblonde@ochsner.org.
authors.forename: Lawrence
authors.initials: L
authors.lastname: Blonde
authors.forename: Michelle A
authors.initials: MA
authors.lastname: Baron
authors.forename: Rong
authors.initials: R
authors.lastname: Zhou
authors.forename: Mary Ann
authors.initials: MA
authors.lastname: Banerji
mesh_terms: D000368:Aged; D001786:Blood Glucose; D002318:Cardiovascular Diseases / Q000453:epidemiology*; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000453:epidemiology*; D004359:Drug Therapy, Combination; D005260:Female; D006442:Glycated Hemoglobin; D006801:Humans; D007003:Hypoglycemia / Q000139:chemically induced*; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D007328:Insulin / Q000627:therapeutic use; D000069036:Insulin Glargine; D049528:Insulin, Long-Acting / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D016032:Randomized Controlled Trials as Topic; D012307:Risk Factors
chemical_list: D001786:Blood Glucose; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007328:Insulin; D000069036:Insulin Glargine; D049528:Insulin, Long-Acting