Prandial premixed insulin analogue regimens versus basal insulin analogue regimens in the management of type 2 diabetes: an evidence-based comparison

Clin Ther. 2007 Jun;29(6 Pt 1):1254-70. doi: 10.1016/j.clinthera.2007.07.003.


Background: Insulin is an effective treatment for type 2 diabetes (T2D), a progressive condition in which insulin deficiency is one of the core defects. When patients with T2D are unable to achieve glycemic goals with diet and oral antihyperglycemic medications, a common starting insulin regimen consists of basal or premixed insulin added to oral antihyperglycemic medications. When glycemic goals are not achieved with the initial insulin regimen, a basal-bolus regimen is necessary.

Objective: This article reviews clinical-trial data on the efficacy and safety profile of prandial premixed insulin analogues (insulin aspart and insulin lispro) compared with basal insulin analogues (insulin glargine, insulin detemir, and insulin lispro protamine suspension), with or without a prandial insulin analogue, in the management of T2D.

Methods: A systematic search of Ovid, MEDLINE, and EMBASE (1995-2007) was performed to identify published randomized controlled trials comparing prandial premixed insulin analogues with basal insulin analogues, with or without prandial insulin, in patients with T2D. The search terms were premixed insulin analogues, premixed insulin, biphasic insulin aspart, insulin aspart 70/30, insulin aspart 50/50, premixed insulin lispro, insulin lispro 75/25, insulin lispro 50/50, glargine, and detemir. Abstracts presented at the 2005 and 2006 meetings of the American Diabetes Association and the European Association for the Study of Diabetes and bibliographies of the identified studies were also reviewed. Predetermined criteria for study inclusion were treatment duration of at least 12 weeks, T2D diagnosed using valid criteria, use of a basal insulin analogue (with or without rapid-acting insulin) as a study comparator, and use of well-accepted end points (eg, glycosylated hemoglobin [HbA(1c)], hypoglycemia, preprandial and postprandial blood glucose).

Results: Of the identified randomized controlled trials, 3 studies compared premixed insulin analogues containing 70% or 75% basal and 30% or 25% rapid-acting insulin analogue with basal insulin analogues only, and 3 studies evaluated premixed insulin analogues containing 50% basal and 50% rapid-acting insulin analogue with basal insulin analogues only. Use of prandial premixed insulin analogues was associated with better overall and postprandial glycemic control. In the studies that compared twice-daily premixed insulin analogues with a basal insulin analogue, changes in HbA(1c) ranged from -1.00% to -2.79% and from -0.42% to -2.36%, respectively (P < 0.01). In the studies that compared thrice-daily premixed insulin analogues with a basal insulin analogue, changes in HbA(1c) ranged from -0.72% to -1.2% and from -0.3% to -0.75%, respectively (P < 0.01). These results were achieved with some increase in overall hypoglycemia, but not in nocturnal or severe hypoglycemia. Doses of the premixed insulin analogues were adjusted during the titration period to achieve glycemic goals.

Conclusions: The results of this systematic review suggest that regimens consisting of prandial premixed insulin analogues, which provide both basal and prandial insulin coverage, may be used as an initial insulin regimen in patients with T2D to enable better overall, preprandial, and postprandial glycemic control compared with a basal insulin analogue regimen alone. Premixed insulin analogues are an effective option for initiating and intensifying insulin therapy in patients with T2D.

Publication types

  • Review
  • Systematic Review

MeSH terms

  • Body Weight
  • Cost-Benefit Analysis
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Evidence-Based Medicine
  • Glycated Hemoglobin A / analysis
  • Humans
  • Hypoglycemia / chemically induced
  • Hypoglycemic Agents / therapeutic use*
  • Insulin / analogs & derivatives*
  • Insulin / therapeutic use*
  • Insulin Aspart
  • Insulin Detemir
  • Insulin Glargine
  • Insulin Lispro
  • Insulin, Long-Acting
  • Randomized Controlled Trials as Topic


  • Glycated Hemoglobin A
  • Hypoglycemic Agents
  • Insulin
  • Insulin Lispro
  • Insulin, Long-Acting
  • hemoglobin A1c protein, human
  • Insulin Glargine
  • Insulin Detemir
  • Insulin Aspart