Elsevier

Endocrine Practice

Volume 17, Issue 5, September–October 2011, Pages 727-736
Endocrine Practice

Original Article
Comparison of 2 Intensification Regimens with Rapid-Acting Insulin Aspart in Type 2 Diabetes Mellitus Inadequately Controlled by Once-Daily Insulin Detemir and Oral Antidiabetes Drugs: The Step-Wise Randomized Study

https://doi.org/10.4158/EP10367.ORGet rights and content

ABSTRACT

Objective

To compare the efficacy and safety of 2 intensification strategies for stepwise addition of prandial insulin aspart in patients with type 2 diabetes mellitus treated with insulin detemir.

Methods

This randomized, controlled, parallel-group, open-label, 48-week trial compared the stepwise addition of insulin aspart to either the largest meal (titration based on premeal glucose values [SimpleSTEP]) or to the meal with the largest prandial glucose increment (titration based on postmeal glucose values [ExtraSTEP]) in patients with type 2 diabetes inadequately controlled on basal insulin and oral antidiabetes drugs. After 12 weeks of basal insulin detemir dosage optimization, participants with a hemoglobin A1 level of 7% or greater entered three 12-week treatment periods with stepwise addition of a first insulin aspart bolus, then a second, and then a third, if hemoglobin A1c remained at 7% or greater after 12 and 24 weeks of treatment, respectively. Endpoints included hemoglobin A1c (primary endpoint), fasting plasma glucose, self-measured plasma glucose, adverse events, and hypoglycemia.

Results

Two hundred ninety-six patients were randomly assigned to treatment with insulin aspart in the SimpleSTEP (n = 150) and ExtraSTEP (n = 146) groups. Hemoglobin A1c decreased by approximately 1.2% in both groups, to 7.5 ± 1.1% (SimpleSTEP) and 7.7 ± 1.2% (ExtraSTEP) at end of trial (estimated treatment difference, SimpleSTEP ExtraSTEP: -0.06% [95% confidence interval, -0.29 to 0.17]). Self-measured plasma glucose levels decreased with both regimens. At trial end, approximately 75% of patients in each group were using 3 prandial injections. The frequency of adverse events and hypoglycemia was low and similar between groups.

Conclusion

The SimpleSTEP and ExtraSTEP strategies for stepwise addition of insulin aspart to 1 or more meals were equally effective at intensifying therapy in patients with type 2 diabetes not achieving glycemic control on basal insulin and oral antidiabetic drugs. (Endocr Pract. 2011;17:727-736)

Section snippets

INTRODUCTION

In type 2 diabetes mellitus, the gradual decline in insulin secretion over time (1) requires the addition of continuous insulin to ongoing oral antidiabetes drugs (OADs) and intensification of this insulin regimen to achieve and maintain appropriate glycemic goals and mitigate diabetesrelated vascular complications (2). While once-daily basal insulin replacement is effective in achieving glycemic goals with minimal weight gain or hypoglycemic risk in many patients (3., 4., 5.), others are

Participants

Eligible participants included individuals aged 18 years or older, with type 2 diabetes for at least 6 months, whose HbA1c level was 7.5% to 10% while on basal insulin

(neutral protamine Hagedorn [NPH] insulin once or twice daily, insulin glargine once daily, or insulin detemir [IDet] once daily) in combination with 1 to 3 OADs. Patients using a-glucosidase inhibitors, glucagonlike peptide 1 mimetics, dipeptidyl-peptidase 4 inhibitors, or more than 1.0 unit/kg of insulin at screening were

RESULTS

Of the 345 participants who entered the run-in period, 296 were randomly assigned to treatment with IAsp in the SimpleSTEP (n = 150) and ExtraSTEP (n = 146) groups (Fig. 1), with both groups displaying similar demographic characteristics (Table 2). Thirteen patients were not randomly assigned after run-in because they reached a target HbA1c level less than 7%. Fewer patients dropped out as the study progressed (26 withdrew during period 1, 21 withdrew during period 2, and 4 withdrew during

DISCUSSION

The present study compared 2 strategies for intensifying diabetes management in patients with long-standing type 2 diabetes inadequately controlled with basal insulin and OADs. A significant improvement in glycemic control was achieved by the sequential addition of prandial IAsp using either a simple strategy (SimpleSTEP) or a more quantitative treatment strategy (ExtraSTEP); this was achieved in a population of patients with long-standing and difficult to manage type 2 diabetes. Although the

CONCLUSION

In conclusion, the sequential addition of prandial IAsp to 1 or more meals improves glycemic control in those who need intensification beyond basal insulin. In this study, a simpler approach (SimpleSTEP) was as effective as the more measured ExtraSTEP strategy.

DISCLOSURE

Dr. Meneghini is a consultant for sanofi-aventis, Biodel, and Novo Nordisk has received grant support from Roche, sanofi-aventis, Novo Nordisk, Medtronic Minimed, and MannKind. Dr. Hermansen is a consultant for Merck, Bristol-Myers Squibb, and Novo Nordisk; has received grant support from sanofi-aventis and Novo Nordisk; and

ACKNOWLEDGMENT

This trial is registered at clinicaltrials.gov as NCT00537303. Results of this study were presented in abstract form at the 70th Scientific Sessions of the American Diabetes Association, Orlando, Florida, June 25-29, 2010, and at the 46th Annual Meeting of the European Association for the Study of Diabetes, Stockholm, Sweden, September 20-24, 2010.

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