A stepwise approach to insulin therapy in patients with type 2 diabetes mellitus and basal insulin treatment failure

Endocr Pract. May-Jun 2011;17(3):395-403. doi: 10.4158/EP10323.OR.

Abstract

Objective: To determine whether 1 or 2 preprandial injections before the meals of greatest glycemic impact can be as effective as 3 preprandial injections in patients with type 2 diabetes mellitus and basal insulin treatment failure.

Methods: This was an open-label, parallel-group, 1:1:1 randomized study of adults with type 2 diabetes mellitus on oral antidiabetic drugs with glycated hemoglobin (A1C) levels of 8.0% or greater. After a 14-week run-in with insulin glargine, patients with an A1C level greater than 7.0% were randomly assigned to 1, 2, or 3 time(s) daily insulin glulisine for 24 weeks. Changes in A1C from randomization to study end; percentage of patients achieving an A1C level less than 7.0%; changes in A1C, fasting glucose concentrations, and weight at individual study points; and safety (adverse events and hypoglycemia) were assessed throughout the study.

Results: Three hundred forty-three of 631 patients (54%) completing the run-in phase with insulin glargine were randomly assigned to treatment arms. During the randomization phase, A1C reductions with insulin glulisine once or twice daily were noninferior to insulin glulisine 3 times daily (confidence intervals: -0.39 to 0.36 and -0.30 to 0.43; P>.5 for both). However, more patients met the target A1C with 3 preprandial injections (46 [46%]) than with 2 injections (34 [33%]) or 1 injection (30 [30%]). Severe hypoglycemia occurred in twice as many patients receiving 3 preprandial injections (16%) compared with those receiving 2 injections (8%) and 1 injection (7%), but these differences did not reach significance.

Conclusion: This study provides evidence that initiation of prandial insulin in a simplified stepwise approach is an effective alternative to the current routine 3 preprandial injection basal-bolus approach.

Trial registration: ClinicalTrials.gov NCT00135083.

Publication types

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

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Algorithms*
  • Blood Glucose / drug effects
  • Blood Glucose / metabolism
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Drug Administration Schedule
  • Female
  • Glycated Hemoglobin A / analysis
  • Humans
  • Hypoglycemic Agents / administration & dosage
  • Hypoglycemic Agents / adverse effects
  • Hypoglycemic Agents / therapeutic use
  • Insulin / administration & dosage
  • Insulin / adverse effects
  • Insulin / analogs & derivatives*
  • Insulin / therapeutic use*
  • Insulin, Long-Acting
  • Male
  • Middle Aged
  • Treatment Failure
  • Young Adult

Substances

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

Associated data

  • ClinicalTrials.gov/NCT00135083