Randomized, 1-year comparison of three ways to initiate and advance insulin for type 2 diabetes: twice-daily premixed insulin versus basal insulin with either basal-plus one prandial insulin or basal-bolus up to three prandial injections

Diabetes Obes Metab. 2014 May;16(5):396-402. doi: 10.1111/dom.12225. Epub 2013 Nov 14.

Abstract

Aim: Many patients with type 2 diabetes mellitus (T2DM) initiate insulin therapy when other treatments fail; how best to do this is poorly defined.

Methods: People with T2DM [n = 588; glycated haemoglobin A1C (A1C) >7.0%, mean baseline 9.4%] were randomized to twice-daily premixed protamine-aspart/aspart insulin (PM - 2), once-daily insulin glargine plus zero to one prandial insulin glulisine injection (G + 1), or insulin glargine plus zero to three prandial injections (G + 3). Insulin was titrated for 60 weeks. Efficacy and safety outcomes were assessed.

Results: Discontinuation rates were 53 of the 194 (27%), 44 of the 194 (23%) and 38 of the 194 (20%), for PM - 2, G + 1 and G + 3. Glycaemic control improved in all groups (A1C 7.2 ± 1.37, 7.1 ± 1.68 and 7.0 ± 1.21% at 60 weeks; 7.5 ± 1.29, 7.2 ± 1.62 and 7.2 ± 1.63% at endpoint). G + 1 was statistically non-inferior to PM - 2 in reducing A1C. G + 3 was slightly superior to PM - 2 in attaining <7.0% at 60 weeks, but only when the analysis included Good Clinical Practice non-adherent sites. Hypoglycaemia with plasma glucose <2.8 mmol/l was more frequent with PM - 2 versus G + 1 and G + 3; [adjusted incidence: 46 (p = 0.0087) vs. 33 (p = 0.0045) and 31.5%; events per patient-year: 1.9 vs. 0.8 and 0.9, p ≤ 0.0001]. Insulin dosage and weight-gain were similar.

Conclusion: Basal insulin plus a single prandial injection is as effective in improving glycaemic control as premixed insulin. Full basal-prandial therapy is only slightly more effective than premixed insulin. Stepwise basal-prandial regimens improve glycaemic control with less hypoglycaemia than twice-daily premixed insulin.

Keywords: basal-bolus; insulin intensification; treat to target.

Publication types

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

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Blood Glucose / metabolism*
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Drug Administration Schedule
  • Drug Therapy, Combination
  • Evidence-Based Medicine
  • Female
  • Glycated Hemoglobin A / metabolism*
  • Humans
  • Hypoglycemia / blood
  • Hypoglycemia / chemically induced
  • Hypoglycemic Agents / administration & dosage*
  • Insulin / administration & dosage*
  • Insulin / analogs & derivatives
  • Male
  • Middle Aged
  • Pioglitazone
  • Sulfonylurea Compounds / administration & dosage*
  • Thiazolidinediones / administration & dosage*
  • Treatment Outcome
  • United States

Substances

  • Blood Glucose
  • Glycated Hemoglobin A
  • Hypoglycemic Agents
  • Insulin
  • Sulfonylurea Compounds
  • Thiazolidinediones
  • hemoglobin A1c protein, human
  • glimepiride
  • Pioglitazone