Improved postprandial glycemic control with Humalog Mix75/25 after a standard test meal in patients with type 2 diabetes mellitus

Clin Ther. 2000 Feb;22(2):222-30. doi: 10.1016/s0149-2918(00)88480-5.


Objective: This double-blind study was designed to compare the postprandial glucodynamic profile of Humalog Mix75/25, a new premixed insulin analogue containing 75% neutral protamine lispro and 25% insulin lispro with that of human insulin 70/30 (70% neutral protamine Hagedorn insulin and 30% regular human insulin) in patients with type 2 diabetes mellitus.

Background: Insulin lispro Mix75/25 (Mix75/25) is the first available insulin formulation in which both the rapid-acting and basal components are insulin analogues.

Methods: This randomized, multicenter, double-blind, crossover study monitored patients' postprandial glucodynamic response to Mix75/25 and human insulin 70/30 (70/30) after a standard test meal. Eighty-four patients with type 2 diabetes participated in this study and were randomly assigned to 1 of 2 treatment sequence groups. Patients received an identical test meal on 4 occasions, completing 2 test meals for each treatment. Equal doses of Mix75/25 or 70/30 were administered 5 minutes before each of the 2 test meals, with doses individualized for each patient. Blood samples were collected for 4 hours after the meal for measurement of plasma glucose. From these plasma glucose measurements, fasting plasma glucose, 2-hour postprandial glucose (2pp), 2-hour postprandial glucose excursion (2pp(ex)), maximum glucose excursion (Gex(max)), the area under the glucose concentration versus time curve from 0 to 4 hours (AUC4), and the area under the glucose excursion versus time curve from 0 to 4 hours (AUCex4) were calculated.

Results: Because of significant differences in the baseline fasting plasma glucose levels between Mix75/25 and 70/30 (Mix75/25: 8.9+/-2.2 mmol/L [160.2+/-39.6 mg/dL]; 70/30: 8.6+/-1.9 mmol/L [154+/-34 mg/dL), analyses of the excursion parameters provide a truer comparison of the glucodynamic response between insulin formulations. Mix75/25 resulted in significantly lower values for 2pp(ex) (3.35+/-2.28 vs 4.13+/-2.26 mmol/L), Gex(max) (4.51+/-1.88 vs 5.19+/-1.98 mmol/L), and AUCex4 (8.01+/-7.02 vs 10.6+/-6.47 mmol x h/L) compared with 70/30.

Conclusions: In patients with type 2 diabetes mellitus, premeal injection of Mix75/25 resulted in better postprandial glycemic control than did premeal injection of 70/30 in the 4 hours after a standard meal. Mix75/25 is a valuable option for managing postprandial blood glucose in patients with type 2 diabetes mellitus who require insulin.

Publication types

  • Clinical Trial
  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Aged
  • Area Under Curve
  • Blood Glucose / drug effects
  • Cross-Sectional Studies
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Double-Blind Method
  • Female
  • Humans
  • Hypoglycemic Agents / administration & dosage
  • Hypoglycemic Agents / pharmacokinetics
  • Hypoglycemic Agents / therapeutic use*
  • Injections, Intravenous
  • Insulin / administration & dosage
  • Insulin / analogs & derivatives*
  • Insulin / pharmacokinetics
  • Insulin / therapeutic use*
  • Insulin Lispro
  • Male
  • Middle Aged
  • Postprandial Period
  • Protamines / administration & dosage
  • Protamines / pharmacokinetics
  • Protamines / therapeutic use


  • Blood Glucose
  • Hypoglycemic Agents
  • Insulin
  • Insulin Lispro
  • Protamines
  • neutral protamine lispro insulin