Insulin lispro low mixture twice daily versus basal insulin glargine once daily and prandial insulin lispro once daily in patients with type 2 diabetes requiring insulin intensification: a randomized phase IV trial

F J Tinahones, J L Gross, A Onaca, S Cleall, A Rodríguez, F J Tinahones, J L Gross, A Onaca, S Cleall, A Rodríguez

Abstract

Aims: To compare the efficacy and safety of two insulin intensification strategies in patients with type 2 diabetes inadequately controlled on basal insulin glargine with metformin and/or pioglitazone.

Methods: A multinational, randomized, open-label trial that compared insulin lispro low mixture (LM25; n = 236) twice daily with a basal-prandial regimen of insulin glargine once daily and insulin lispro once daily (IGL; n = 240) over 24 weeks in patients with HbA1c 7.5-10.5% and fasting plasma glucose ≤ 6.7 mmol/l. The primary objective was to assess non-inferiority [per-protocol (PP) population], and then superiority [intention-to-treat (ITT) population], of LM25 versus IGL according to change in HbA1c after 24 weeks (non-inferiority margin 0.4%, two-sided significance level 0.05).

Results: Estimated change [least squares (LS) mean (95% CI)] in HbA1c after 24 weeks: -1.30 (-1.44, -1.16)% with LM25 and -1.08 (-1.22, -0.94)% with IGL. Non-inferiority was shown [LS mean (95% CI) HbA1c treatment difference -0.21 (-0.38, -0.04) (PP population)]; gated superiority assessment showed a statistically significant advantage for LM25 (p = 0.010; ITT population). Mean blood glucose, glycaemic variability, overall tolerability and hypoglycaemic episodes per patient-year did not show significant differences between treatments during the study.

Conclusions: In patients with type 2 diabetes inadequately controlled on once-daily basal insulin glargine and metformin and/or pioglitazone, intensification with LM25 was superior to a basal-prandial approach in terms of reduction in HbA1c after 24 weeks and did not increase hypoglycaemia episodes.

Trial registration: ClinicalTrials.gov NCT01175824.

Keywords: insulin glargine; insulin intensification; insulin lispro; insulin lispro mixture; type 2 diabetes.

© 2014 The Authors. Diabetes, Obesity and Metabolism published by JohnWiley & Sons Ltd.

Figures

Figure 1
Figure 1
Summary of patient disposition. *Insulin lispro low mixture (insulin lispro protamine suspension 75% and insulin lispro solution 25%) twice daily; basal insulin glargine once daily and prandial insulin lispro once daily.
Figure 2
Figure 2
Glycaemic control throughout the study for the intention-to-treat population receiving insulin lispro low mixture (LM25; insulin lispro protamine suspension 75% and insulin lispro solution 25%) twice daily or basal insulin glargine once daily and prandial insulin lispro once daily (IGL). (a) Box plot of unadjusted HbA1c levels, showing median values (horizontal line) and interquartile range (shaded box), with minimum and maximum values (whiskers) and mean values (diamond) at baseline, and 12 and 24 weeks. (b) Mean unadjusted 7-point self-monitoring of blood glucose levels at baseline and 24 weeks. *At 12 and 24 weeks, self-monitoring of blood glucose (SMBG) levels estimated using a likelihood-based mixed model for repeated measure analysis were significantly lower in the IGL group before breakfast (p

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