Personalized intensification of insulin therapy in type 2 diabetes – does a basal–bolus regimen suit all patients?

Abstract

Many patients with type 2 diabetes mellitus (T2DM) require insulin therapy. If basal insulin fails to achieve glycemic control, insulin intensification is one possible treatment intensification strategy. We summarized clinical data from randomized clinical trials designed to compare the efficacy and safety of basal–bolus and premixed insulin intensification regimens. We defined a between-group difference of ≥0.3% in end-of-study glycated hemoglobin (HbA_1c) as clinically meaningful. A PubMed database search supplemented by author-identified papers yielded 15 trials which met selection criteria: randomized design, patients with T2DM receiving basal–bolus (bolus injection ≤3 times/day) vs. premixed (≤3 injections/day) insulin regimens, primary/major endpoint(s) HbA_1c- and/or hypoglycemia-related, and trial duration ≥12 weeks. Glycemic control improved with both basal–bolus and premixed insulin regimens with – in most cases – acceptable levels of weight gain and hypoglycemia. A clinically meaningful difference between regimens in glycemic control was recorded in only four comparisons, all of which favored basal–bolus therapy. The incidence of hypoglycemia was significantly different between regimens in only three comparisons, one of which favored premixed insulin and two basal–bolus therapy. Of the four trials that reported a significant difference between regimens in bodyweight change, two favored basal–bolus therapy and two favored premixed insulin. Thus, on a population level, neither basal–bolus therapy nor premixed insulin showed a consistent advantage in terms of glycemic control, hypoglycemic risk, or bodyweight gain. It is therefore recommended that clinicians should adopt an individualized approach to insulin intensification – taking into account the benefits and risks of each treatment approach and the attitude and preferences of each patient – in the knowledge that both basal–bolus and premixed regimens may be successful.

Key words:

• Basal–bolus
• Insulin intensification; Personalized; Premixed; Type 2 diabetes mellitus

Transparency

Declaration of funding

This article was funded by Eli Lilly and Company.

Declaration of financial/other relationships

D.G. has disclosed that he lectures for Eli Lilly and Sanofi Aventis, and received consultancy fee from Eli Lilly. J.S. has disclosed that she/he lectures and receives support for travel to meetings from MSD, Novartis and Bioton Poland, and is on Advisory Boards for MSD, Novartis, Bioton Poland and Eli Lilly and Company. A.S. and R.G. have disclosed that they are full-time employees of Eli Lilly and Company.

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

Acknowledgments

The authors wish to acknowledge Dr. Janet Douglas and Caroline Spencer (Rx Communications, Mold, UK) for medical writing assistance with the preparation of this article, funded by Eli Lilly and Company.