Biphasic Insulin Aspart in Type 2 Diabetes Mellitus: An Evidence-Based Medicine Review

S.C.L. Gough; J. Tibaldi


Clin Drug Invest. 2007;27(5):299-324. 

In This Article

Abstract and Introduction

The efficacy benefits of biphasic insulin aspart formulation (BIAsp 30) in patients with diabetes mellitus have been reported in several studies. BIAsp 30 has been shown to be more effective in terms of glycaemic control than standard biphasic human insulin 30 (BHI 30). In addition to gauging the treatment in terms of clinical evidence of benefits provided, it is also important to evaluate the strength of the evidence supporting the therapeutic improvements offered by BIAsp 30. In this paper, we evaluated the strength of the available data that relate to the use of BIAsp 30 in the treatment of patients with type 2 diabetes based on a comprehensive literature review. Selected publications that provided relevant data were obtained via a literature search and from the manufacturer, Novo Nordisk. These were graded in terms of the strength of the evidence they provided using the Oxford Centre for Evidence-Based Medicine (CEBM) system in the following categories: (i) twice-daily use versus basal insulin; (ii) twice-daily use versus other treatments; (iii) once-daily use; (iv) thrice-daily use; (v) use in combination with thiazolidinediones; and (vi) use in comparison with BHI 30. A total of 30 publications for BIAsp 30 were identified and graded. For the majority of categories (four out of six), the evidence supporting the use of BIAsp 30 was given an overall CEBM grade of A (highest quality); evidence supporting clinical efficacy in the other two categories (twice-daily use versus basal insulin and thrice-daily BIAsp 30 administration) was graded B.

In most of the studies examined, the efficacy of BIAsp 30 was evaluated in terms of glycaemic control (glycosylated haemoglobin [HbA1c] reduction, proportion of patients achieving HbA1c target of <6.5% or <7%, fasting blood glucose, blood glucose profile and/or prandial and postprandial glucose increments). In some studies, efficacy was further evaluated using plasma insulin and glucose infusion rates, plasma C-peptide levels, mean serum fructosamine levels, postprandial hyperlipidaemia, overall well-being, treatment satisfaction and quality of life. Safety was evaluated using physical and laboratory investigations and assessment of incidence of adverse events, including, in many of the studies reviewed, specific evaluation of those events known to be associated with antidiabetic treatment, hypoglycaemia and weight gain. Strong evidence was provided for better glycaemic control with BIAsp 30 without increases in the incidence of major hypoglycaemia or nocturnal hypoglycaemic episodes. Overall, weight gain with BIAsp 30 was minimal and not significantly greater than with basal insulin or BHI 30.

Thus, we can confirm that the reported efficacy and tolerability of BIAsp 30 in the treatment of diabetes based on a variety of clinical endpoints is supported by a good body of evidence relating to its use in different dosage regimens and in comparison with other insulin treatment regimens.

Diabetes mellitus is one of the most serious global healthcare problems, with the global prevalence set to rise from 171 million cases in 2000 to 366 million by 2030.[1] Moreover, the prevalence of type 2 diabetes, which accounts for around 90% of cases, is rising in both adults and children.[2,3] Complications associated with diabetes add to the burden, although they may be avoided or delayed with maintenance of near-normal glycaemic control.[4,5] Postprandial glucose excursions make a major contribution to overall glycaemic control and may be involved in the development of diabetes complications, particularly cardiovascular complications.[6] Indeed, the impact of postprandial glucose control on overall glycaemic control appears to increase as glycosylated haemoglobin (HbA1c) values approach American Diabetes Association (ADA) target levels of <7% and American College of Endocrinology (ACE) and International Diabetes Federation (IDF) targets of =6.5%.[7,8]

In patients with uncontrolled type 2 diabetes, early initiation of insulin therapy is recommended to supplement the inability of oral antidiabetic drugs alone to prevent deterioration of metabolic control. While an intensive insulin regimen can effectively reduce and delay complications,[9,10] for some patients such multiple injection regimens can be a burden on their lifestyle, which may impact on adherence. Since patients who retain some capacity for insulin secretion may not require such an intensive approach, many may prefer a once- or twice-daily regimen using biphasic premixed insulin. In addition, with this approach both prandial and basal aspects of glucose regulation are addressed and dosage errors may be reduced by avoiding self-mixing of insulin preparations.

Previously, biphasic human insulin 30 (BHI 30), comprising 30% soluble human insulin and 70% insulin suspension isophane (neutral protamine Hagedorn [NPH] insulin), has been the most widely used premix preparation. However, BHI 30 shares many of the limitations of unmodified human insulin, and the delayed absorption of the soluble insulin component results in limited postprandial glucose control. Additionally, adherence to the recommended 30- to 45-minute preprandial injection interval for human insulin may not be observed.[11] Insulin analogues were developed to address the difficulties associated with human insulin. Rapid-acting analogues (e.g. insulin aspart) have a shorter onset and duration of action and can be given immediately before meals.[12]

A biphasic formulation of insulin aspart has been developed, comprising 30% rapid-acting soluble insulin aspart and 70% intermediate-acting protaminated insulin aspart (BIAsp 30; also known as BIAsp 70/30 in the US). This insulin formulation has a more rapid onset of action than BHI 30,[13] allowing it to be given closer to a meal (within 0–10 minutes before or after starting the meal). In contrast to what is often considered characteristic of premixed insulins, BIAsp 30 produces a protracted decline in glucose-lowering activity after initial rapid onset, without a second separate insulin peak.[14]

The aim of the current paper is to review the literature and evaluate (using the Oxford Centre for Evidence-Based Medicine [CEBM] approach) the strength of the available published evidence on the use of BIAsp 30 in patients with type 2 diabetes in various categories.


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