Effects of initiation and titration of a single pre-prandial dose of insulin glulisine while continuing titrated insulin glargine in type 2 diabetes: a 6-month 'proof-of-concept' study

Diabetes Obes Metab. 2011 Nov;13(11):1020-7. doi: 10.1111/j.1463-1326.2011.01459.x. Epub 2011 Sep 2.


Aim: Stepwise intensification of insulin treatment to match the progressive decline of endogenous insulin secretion has been shown to be an effective management strategy in type 2 diabetes mellitus (T2DM). The efficacy of initiating and titrating a single bolus dose of insulin glulisine to baseline insulin glargine plus oral hypoglycaemic agents (OHAs) was investigated.

Methods: This was a 6-month, parallel-group, randomized, open-label, Phase IV study conducted in the US, UK and Russia. People with T2DM (HbA(1c) 7.5-9.5%) using any basal insulin underwent a 3-month run-in period on insulin glargine titrated to optimize fasting blood glucose (BG) control. Those with HbA(1c) >7.0% were randomized to either continue prior therapy (n = 57) or to add a single dose of insulin glulisine (n = 49) immediately prior to the main meal for a further 3 months. Two different titration algorithms were employed for the bolus dose, targeting 2-h postprandial BG ≤135 mg/dL (≤7.5 mmol/l; Russia and UK) or pre-meal/bedtime BG 100-120 mg/dl (5.5-6.7 mmol/l; US).

Results: HbA(1c) and fasting plasma glucose levels decreased during the run-in period. In the 3 months after randomization, more participants in the basal-plus-bolus group reached HbA(1c) <7.0% than the basal-only control group (22.4 vs. 8.8%; p < 0.05), with significantly greater reduction of HbA(1c) (-0.37 vs. -0.11%; p = 0.0290). Rates of hypoglycaemia and mean weight change were comparable between the treatment groups.

Conclusions: In people with T2DM inadequately controlled on basal insulin plus OHAs, adding a single injection of insulin glulisine prior to the main meal significantly improves glucose control without undesired side effects.

Publication types

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

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Algorithms
  • Biomarkers / blood
  • Blood Glucose / drug effects
  • Blood Glucose / metabolism
  • Body Mass Index
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetes Mellitus, Type 2 / epidemiology
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Fasting
  • Female
  • Glycated Hemoglobin A / drug effects
  • Glycated Hemoglobin A / metabolism
  • Humans
  • Hypoglycemic Agents / administration & dosage*
  • Insulin / administration & dosage
  • Insulin / analogs & derivatives*
  • Insulin Glargine
  • Insulin, Long-Acting / administration & dosage*
  • Male
  • Middle Aged
  • Postprandial Period*
  • Russia / epidemiology
  • Treatment Outcome
  • United Kingdom / epidemiology
  • United States / epidemiology
  • Young Adult


  • Biomarkers
  • Blood Glucose
  • Glycated Hemoglobin A
  • Hypoglycemic Agents
  • Insulin
  • Insulin, Long-Acting
  • Insulin Glargine
  • insulin glulisine