Efficacy and safety of a premixed versus a basal-plus insulin regimen as intensification for type 2 diabetes by timing of the main meal

Abstract

Objective: To describe the efficacy and safety of premixed insulin lispro protamine suspension 75%/insulin lispro solution 25% (LM25) twice daily (bid) versus basal insulin glargine plus prandial insulin lispro (IGL), both once daily, according to main meal timing. Methods: Data were obtained post hoc from a 24 week, randomized, open-label study comparing LM25 and IGL as insulin intensification in patients with type 2 diabetes inadequately controlled with once daily basal insulin glargine plus metformin and/or pioglitazone (ClinicalTrials.gov identifier: NCT01175824). Patients administered LM25 bid before breakfast and the evening meal, insulin glargine at bedtime and insulin lispro before the day’s main meal (meal with the highest 2 hour postprandial glucose level during screening). Patients were grouped by main meal. Changes in glycosylated hemoglobin (HbA1c) and bodyweight were summarized using likelihood-based mixed models; hypoglycemia incidence was compared between treatments using Fisher’s exact test. Results: Overall, 476 patients (LM25, n = 236; IGL, n = 240) were randomized. In all main meal groups, with both insulin regimens, mean HbA1c significantly decreased from baseline to 24 weeks (p < 0.0001). Patients whose main meal was in the evening had a greater bodyweight increase with LM25 than with IGL (p = 0.015), and a smaller proportion of these patients experienced total (p = 0.027) and nocturnal (p = 0.006) hypoglycemia with LM25 compared with IGL. Patients whose main meal was lunch experienced more nocturnal hypoglycemia with LM25 than with IGL (p = 0.030). Study limitations include that this was a post hoc analysis and no assessments ensured that: SMBG results determined timing of the main meal, each patient’s main meal remained unchanged throughout the study, or patients administered insulin lispro with that meal. Conclusions: Glycemic control improved in patients receiving either LM25 or IGL, irrespective of main meal timing. Both regimens can be used in patients with inadequate glycemic control who are in need of insulin intensification.

Keywords:

• Insulin glargine
• Insulin intensification
• Insulin lispro mixture
• main meal
• prandial insulin lispro
• type 2 diabetes

Declaration of funding

The study was funded by Eli Lilly.

Author contributions: J.L.G. contributed to acquisition, analysis, interpretation of data and supervision of the work. A.R. contributed to acquisition, analysis, and interpretation of data for the work and conducting the protocol. S.S. contributed to acquisition, analysis, interpretation of data and administrative, technical/material support for the work. F.J.T. contributed to acquisition, analysis, interpretation of data and supervision of the work. S.C. contributed to acquisition, analysis, and interpretation of data for the work, drafting of the manuscript and statistical analysis. A.R. contributed to conception and design of the work, acquisition, analysis, and interpretation of data, drafting of the manuscript and supervision of the work. All authors have critically revised the manuscript for intellectual content and approved it for submission.

Declaration of financial/other relationships

A.Rz. and S.C. have disclosed that they are employees of and shareholders in Eli Lilly and Company. J.L.G. has disclosed that he has received grants/research support from Boehringer Ingelheim, Bristol-Myers Squibb, Eli Lilly and Company and Novo Nordisk, and has served as a consultant or member of a scientific advisory panel/speakers bureau for Boehringer Ingelheim, Bristol-Myers Squibb, Eli Lilly and Company and Novo Nordisk. F.J.T. has disclosed that he has served on scientific advisory boards and received honoraria or consulting fees or grants/research support from AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Eli Lilly and Company, GlaxoSmithKline, Hoffmann-La Roche, Merck Serono, MSD, Novartis, Novo Nordisk and Sanofi. S.S. has disclosed that he has served as a member of a scientific advisory panel/speakers bureau for Boehringer Ingelheim, Eli Lilly, Merck Serono and Sanofi. A.Rs. has disclosed that he has no significant relationships with or financial interests in any commercial companies related to this study or article.

CMRO peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Acknowledgments

The authors thank Caroline Spencer and Janet Douglas (Rx Communications, Mold, UK) for medical writing assistance during the preparation of this manuscript, funded by Eli Lilly.

Previous presentation: Results of this analysis were presented, in part, at the 10th International Diabetes Federation – Western Pacific Region Congress, 21–24 November 2014, Suntec, Singapore.