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.

Author(s): Owens DR, Luzio SD, Sert-Langeron C, Riddle MC

Affiliation(s): Diabetes Research Unit, Cardiff University, University Hospital Llandough, Penarth, UK. owensdr@cardiff.ac.uk

Publication date & source: 2011-11, Diabetes Obes Metab., 13(11):1020-7. Epub 2011 Sep 2.

Publication type: Clinical Trial, Phase IV; Multicenter Study; Randomized Controlled Trial; Research Support, Non-U.S. Gov't

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. (c) 2011 Blackwell Publishing Ltd.