Review ArticleRapid-Acting Insulin Analogues in Basal-Bolus Regimens in Type 1 Diabetes Mellitus
Section snippets
INTRODUCTION
In healthy persons, insulin is secreted basally and in response to the ingestion of carbohydrate-containing food. Peaks in secretion occur shortly after meals (1, 2) to maintain blood glucose levels within the range of 63 to 126 mg/ dL (Fig. 1) (2). However, in persons with type 1 diabetes mellitus, β-cell function is severely compromised from the beginning of the disease (1, 3). Therefore, insulin therapy is essential for the treatment of type 1 diabetes to man- age basal and postprandial
METHODS
We performed a MEDLINE search to identify all pub- lished randomized controlled studies that compared an RAIA (ie, aspart, glulisine, or lispro) with either RHI or an alternative insulin analogue in patients with type 1 diabe- tes. We included studies in all age groups and populations, except studies of the highly specific patient population of pregnant women with type 1 diabetes. We also excluded observational studies, inpatient studies, and pharmacoki- netic/pharmacodynamic studies. In
Rapid-Acting Insulin Analogues in Basal-Bolus Therapy in Type 1 Diabetes
Overall, in the MEDLINE search, we identified 151 studies on RAIA in subjects with type 1 diabetes. A total of 126 studies were excluded for the following reasons: 36 studies comprised subjects with type 2 diabetes, 31 studies evaluated CSII, 19 studies evaluated premixed insulin, 16 studies evaluated basal insulin therapy, 10 studies included pregnant women, 7 studies evaluated a regimen other than basal-bolus, and 7 studies were observational. One study was associated with 2 articles, which
DISCUSSION
The 3 RAIAs offer advantages over RHI in terms of lowering postprandial hyperglycemia. However, the stud- ies identified in this literature review do not prove that this translates to a significant reduction in HbA1c levels. There are several possible explanations for this observation. First, many of the studies have been performed with NPH as a “basal” insulin. Because of the limitations of NPH insu- lin in providing a stable coverage of the basal insulin need in type 1 diabetes, the reduced
CONCLUSION
The results of the studies identified in this literature review suggest that a basal-bolus regimen with prandial RAIA provides advantages over basal-bolus regimens us- ing prandial RHI, with respect to HbA1c reduction and low- er incidence of hypoglycemia. This advantage may be at least partly attributable to the improved pharmacokinetic/ pharmacodynamic properties that allow for more accurate reproduction of endogenous insulin secretion patterns. Comparison of RAIA-based basal-bolus regimens
DISCLOSURE
Dr. Satish Garg, Dr. Martin Pfohl, and Dr. Francisco Javier Ampudia-Blasco have received research grants from NovoNordisk and sanofi-aventis. Dr. Garg and Dr. Ampudia-Blasco have also received research grants from Eli Lilly and Co, and Dr. Pfohl has received research grants from Pfizer.
ACKNOWLEDGMENT
Thisstudy was sponsored by sanofi-aventis. Editorial support for this article was provided by the Global Publications Group of sanofi-aventis.
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