Six-month multicentric, open-label, randomized trial of twice-daily injections of biphasic insulin aspart 30 versus multiple daily injections of insulin aspart in Japanese type 2 diabetic patients (JDDM 11)

doi:10.1016/j.diabres.2007.08.011

Diabetes Research and Clinical Practice

Volume 79, Issue 1, January 2008, Pages 171-176

https://doi.org/10.1016/j.diabres.2007.08.011 Get rights and content

Abstract

To evaluate glycemic control using convenience-oriented biphasic insulin analog compared with intensified insulin therapy, we conducted a 6-month multicentric, open-label, randomized trial in Japanese insulin-naïve patients with type 2 diabetes mellitus. A total of 160 adult patients at 19 centers were randomized into two groups: those who received twice-daily injections of biphasic insulin aspart 30 and those on three-times-daily injections of insulin aspart with or without NPH insulin (multiple daily injections). At 6 months, mean HbA_1c decreased by approximately 2.5% in both groups. Reduction of HbA_1c on both regimens was better in patients whose prior therapy before starting the study was only diet and exercise (−5.0%) than in patients who were previously taking oral antidiabetic agents (−1.0%). No incidence of major hypoglycemia was observed in either regimen. These results suggest that convenience-oriented insulin therapy using biphasic insulin analog is as useful as intensified insulin therapy with insulin analog for the treatment of type 2 diabetes mellitus over 6 months. Furthermore, early induction of insulin therapy in individuals hitherto using only diet and exercise may provide good glycemic control. This study suggests that convenience-oriented biphasic insulin aspart 30 might be a useful option for the treatment of type 2 diabetes mellitus, especially for insulin-naïve patients over 6 months, although it should be changed to another regimen when expected efficacy is not obtained.

Introduction

Many studies have shown that strict glycemic control is one of the most important factors in the management of diabetes mellitus to prevent risk of death from diabetic complications and cardiovascular diseases. The Diabetes Control and Complication Trial (DCCT) [1] showed that intensified insulin therapy using a regimen consisting of three-times-daily injections of regular insulin with or without NPH insulin provides better glycemic control than convenience-oriented insulin therapy using twice-daily human insulin in patients with type 1 diabetes mellitus. Furthermore, Ohkubo et al. [2] reported similar results in patients with type 2 diabetes mellitus.

The increasing incidence of type 2 diabetes mellitus in Japan is believed to reflect shifting diet and lifestyle changes among the general population. As a result, it is increasingly necessary to select therapeutic regimens that not only effectively maintain glycemic control but also allow diabetic patients to pursue many daily activities; in large numbers of insulin-requiring diabetic patients, multiple-daily injection regimens are not desirable. In this regard, in many outpatients overall glycemic control attained with twice-daily injection regimens may be as effective as that with multiple injection therapy [3], [4].

Recently, rapid-acting and biphasic insulin analogs have been made available and are being widely used for the treatment of type 2 diabetes mellitus. These insulin analogs are very convenient tools for adjusting to the variety of lifestyles of today's diabetic patients. However, among modern insulin analog therapies it is not known whether rapid-acting analog plus NPH insulin or twice-daily biphasic insulin analog provides better glycemic control.

In 2001, the Japan Diabetes Clinical Data Management Study Group (JDDM) was established to promote clinical research on diabetes in Japan [5]. Data on patients at healthcare institutes across Japan are collected in the CoDiC^® database, a data collection and diabetes management information system developed by the JDDM [5]. The CoDiC^® system enables researchers to perform many multicentric, randomized clinical studies in Japan. Using this database, we performed a multicentric, open-label, randomized trial comparing glycemic control using twice-daily injections of biphasic insulin aspart 30 versus three-times-daily injections of insulin aspart with or without NPH insulin in insulin-naïve patients with type 2 diabetes mellitus.

Section snippets

Subjects

This was a 6-month, randomized controlled trial analyzing data on adult type 2 diabetic patients recruited at 19 centers in Japan. The definition of type 2 diabetes mellitus was based on the criteria in the “Report of the Committee of Japan Diabetes Society (JDS) on the Classification and Diagnostic Criteria of Diabetes Mellitus” [6]. These criteria are almost identical to those described by WHO [7]. Subjects had to have HbA_1c ≥ 8.0% for ≥3 months irrespective of using oral antidiabetic agents

Results

A total of 160 patients were equally randomized to the two treatment groups. At baseline, demographic and clinical characteristics were comparable between the two groups (Table 1). Fifty of the 80 patients (62.5%) in the multiple daily injection group used NPH insulin in addition to insulin aspart. In all, 56 of 80 patients (70.0%) in the twice-daily injection group and 61 of 80 patients (76.3%) in the multiple daily injection group completed the study. The reasons for discontinuation are

Discussion

In this study mean HbA_1c decreased by approximately 2.5% after patients had received either twice-daily injections of biphasic insulin aspart or multiple daily injections of insulin aspart with or without NPH insulin at 6 months. These results are comparable to those of previous studies that suggested that glycemic control using twice-daily injection regimens may be as good as that achieved with multiple daily injection therapy in certain patients [3], [4]. In our study, including data on a

Acknowledgment

This study (JDDM 11) was supported by a grant from the Japan Diabetes Foundation.

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¹: See Appendix A.

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Six-month multicentric, open-label, randomized trial of twice-daily injections of biphasic insulin aspart 30 versus multiple daily injections of insulin aspart in Japanese type 2 diabetic patients (JDDM 11)

Abstract

Introduction

Section snippets

Subjects

Results

Discussion

Acknowledgment

Diabetes Res. Clin. Pract.

Diabetes Res. Clin. Pract.

Diabetes Res. Clin. Pract.

Adv. Drug Deliv. Rev.

The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus

N. Engl. J. Med.

Comparison of conventional twice-daily subcutaneous insulin administration and a multiple injection regimen (using the NovoPen™) in insulin-dependent diabetes mellitus

Diabetes Res.

Comparison of insulin regimens in patients with non-insulin-dependent diabetes mellitus

N. Engl. J. Med.

Definition, diagnosis and classification of diabetes mellitus and its complications. Part 1. Diagnosis and classification of diabetes provisional report of a WHO consultation

Diabetic Med.

Insulin aspart vs. human insulin in the management of long-term blood glucose control in type 1 diabetes mellitus: a randomized controlled trial

Diabetic Med.