Comparative effectiveness of basal-bolus versus premix analog insulin on glycemic variability and patient-centered outcomes during insulin intensification in type 1 and type 2 diabetes: a randomized, controlled, crossover trial

J Clin Endocrinol Metab. 2012 Oct;97(10):3504-14. doi: 10.1210/jc.2012-1763. Epub 2012 Jul 31.

Abstract

Context: In patients with diabetes, intraday glucose variability might predict health outcomes independently from glycosylated hemoglobin (HbA1c).

Objective: Our objective was to evaluate patient satisfaction (PS), quality of life (QoL), glycemic control, and variability during insulin intensification to HbA1c below 7.0%.

Patients, design, and setting: Eighty-two type 1 and 306 insulin-treated type 2 diabetes patients (47% male; age 54±11 yr; HbA1c=7.8±0.7%) participated in this multicenter, randomized, crossover trial at 52 U.S. centers.

Interventions: Interventions included insulin glargine plus premeal glulisine (n=192) vs. twice-daily premix 75/25 or 70/30 analog insulin (n=196) for 12 wk and crossed to the alternate arm for 12 wk.

Main outcome measures: Main outcome measures included PS and QoL questionnaires, 3-d continuous glucose monitoring (CGM), and HbA1c every 4-8 wk.

Results: Mean±se HbA1c change was -0.39±0.09% for glargine-glulisine and -0.05±0.09% for premix (P<0.0001). The PS net benefit scale (0-100) improved from 51.1 to 60.5±1.2 for glargine-glulisine and worsened to 45.4±1.2 for premix (P<0.0001). The PS regimen acceptance scale was comparable (P=0.33). Overall QoL favored glargine-glulisine (P<0.001), as did perceived health (P<0.0001), symptom distress (P<0.0001), general health perceptions (P<0.01), and psychosocial (P<0.02). CGM daily glucose mean, daily glucose sd (glycemic variability), and percent time over 140 mg/dl were lower for glargine-glulisine by 13.1±2.7 mg/dl, 5.9±1.4 mg/dl, and 7.3±1.6%, respectively (all P<0.0001), with no difference in CGM percent time below 70 mg/dl (P=0.09). Symptomatic hypoglycemia rates were comparable. HbA1c, mean CGM daily glucose, and glycemic variability were independent predictors of PS net benefit.

Conclusions: Patient satisfaction was impacted more positively by improved QoL, reduced glucose variability, and better glycemic control with a basal-bolus regimen than negatively by the burden of additional injections, thereby facilitating insulin intensification and the ability to achieve HbA1c below 7.0%.

Trial registration: ClinicalTrials.gov NCT00135941.

Publication types

  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Blood Glucose / drug effects
  • Body Weight / drug effects
  • Cross-Over Studies
  • Diabetes Mellitus, Type 1 / drug therapy*
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Female
  • Follow-Up Studies
  • Glycated Hemoglobin A / metabolism
  • Humans
  • Hypoglycemia / chemically induced
  • Hypoglycemic Agents / administration & dosage*
  • Hypoglycemic Agents / adverse effects
  • Insulin / administration & dosage
  • Insulin / adverse effects
  • Insulin / analogs & derivatives*
  • Insulin Glargine
  • Insulin, Long-Acting / administration & dosage*
  • Insulin, Long-Acting / adverse effects
  • Male
  • Middle Aged
  • Patient Satisfaction
  • Quality of Life
  • Surveys and Questionnaires

Substances

  • Blood Glucose
  • Glycated Hemoglobin A
  • Hypoglycemic Agents
  • Insulin
  • Insulin, Long-Acting
  • hemoglobin A1c protein, human
  • Insulin Glargine
  • insulin glulisine

Associated data

  • ClinicalTrials.gov/NCT00135941