Predictors of achieving HbA_1c <7% and no hypoglycaemia 6 months after initiation of biphasic insulin aspart 30 in patients with type 2 diabetes in the IMPROVE study

Abstract

Background:

Early initiation of insulin therapy has widely been associated with numerous benefits, including improved glycaemic control and reduced long-term risk of developing microvascular diseases. Biphasic insulins offer a convenient option for insulin initiation, addressing both basal and postprandial insulin requirements with one injection, making them relatively simple for patients to dose. Development of biphasic insulin aspart (BIAsp) has further offered improved postprandial glycaemic control and lower rates of nocturnal and major hypoglycaemia than biphasic human insulin.

Methods:

The safety and efficacy of the 30/70 rapid-acting/intermediate-acting formulation of BIAsp (BIAsp 30) in patients with type 2 diabetes was examined in the IMPROVE study, a 26-week, international, observational trial. In this subanalysis, baseline clinical factors that predicted treatment success, defined as HbA_1c <7% (<53 mmol/mol) without experiencing hypoglycaemia after 26 weeks on BIAsp 30 therapy, were assessed.

Results:

The composite endpoint was defined for 44,010 (77%) patients from the total cohort of 57,478, and 28,696 of these were included in the statistical examination. The results of the analysis suggest that those with lower baseline HbA_1c of ≤8% (≤64 mmol/mol), shorter duration of diabetes at baseline (<5 years) and no incidence of major hypoglycaemia at 13 weeks, or minor hypoglycaemia at 4 weeks, before the beginning of the trial were more likely to achieve treatment success.

Conclusion:

Lower baseline HbA_1c, shorter duration of diabetes and no incidence of hypoglycaemia up to 13 weeks prior to initiation are predictors of achieving HbA_1c <7% without hypoglycaemia with a BIAsp 30 regimen. These results suggest that it is easier to reach target without hypoglycaemia with BIAsp 30 when prescribed earlier. As this was an observational study, lack of control groups or randomisation, as well as varying clinical practices in study countries, potentially introduced bias.

Trial registration:

ClinicalTrials.gov identifier: NCT00659282.

Keywords::

• Biphasic insulin aspart 30
• Clinical inertia
• Insulin therapy
• Type 2 diabetes

Transparency

Declaration of funding

This subanalysis of the IMPROVE study was sponsored by Novo Nordisk A/S, Denmark.

Declaration of financial/other relationships

P.V. has served as principal investigator in the IMPROVE study and given lectures for Novo Nordisk. He is a board member at Daiichi-Sankyo, Bristol Myers Squibb, Glaxo Smithkline and Merck Sharp Dohme. His research was granted by Merck Santé, Glaxo Smithkline, Novo Nordisk, Bayer, Abbott, Bristol Myers Squibb/Astra Zeneca. J.S. has worked on the advisory panel for Abbott Diabetes Care, Eli Lilly and Company and Genzyme. He has also provided research support for Eli Lilly and Company, Merck, Novo Nordisk A/S and Sanofi and additionally received honoraria as a speaker for Abbott Diabetes Care, Boehringer Ingelheim, Bristol-Myers Squibb Company, Eli Lilly and Company, Novo Nordisk A/S, Sepracor Pharmaceuticals and Solvay Pharma. S.S. is an advisory panel board member for Novo Nordisk A/S. M.B. has provided research support for Eli Lilly and Company, Novo Nordisk A/S, Roche Pharmaceuticals and Sanofi. R.K. received consultancy fees, a research grant and honoraria for lectures from NovoNordisk Japan. V.B. has provided research support for Novo Nordisk A/S. Y.W. has disclosed that he/she has no significant relationships with or financial interests in any commercial companies related to this study or article. V.P. and J.B.H. are employees of Novo Nordisk A/S. J.G. has worked as a consultant for Bioton, Bristol-Myers Squibb Company, Eli Lilly and Company, Merck and Polpharma. He has received honoraria as a speaker for Bioton, Eli Lilly and Company, Merck, Merck Sharp and Dohme Limited, Polpharma, Roche Pharmaceuticals, Sanofi and Servier.

CMRO peer reviewers may have received honoraria for their review work. The peer reviewers on this manuscript have disclosed that they have no relevant financial relationships.

Acknowledgements

We would also like to thank Watermeadow Medical for their editorial assistance, financed by Novo Nordisk A/S, Denmark.

Previous presentation: Valensi P, Kawamori IR, Shaban JA et al.; IMPROVE Study Expert Panel. Predictors of the composite endpoint (A1C <7%, weight change ≤0 kg and no hypoglycemia) at 6 months following the initiation of biphasic insulin aspart 30 (BIAsp 30) in patients with type 2 diabetes (T2D) on prior oral antidiabetic drug therapy. Diabetes 2011;60:617-18, Abstract 2321-PO.