Original ArticleComparison 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
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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