Elsevier

Endocrine Practice

Volume 16, Issue 3, May–June 2010, Pages 486-505
Endocrine Practice

Review Article
Rapid-Acting Insulin Analogues in Basal-Bolus Regimens in Type 1 Diabetes Mellitus

https://doi.org/10.4158/EP09294.RAGet rights and content

ABSTRACT

Objective

To compare rapid-acting insulin analogues with regular human insulin in terms of hemoglobin A1c, hypoglycemia, and insulin dose when used in a basal-bolus regimen in patients with type 1 diabetes mellitus.

Methods

MEDLINE and congress proceedings were searched for randomized controlled trials comparing pran- dial insulins in a basal-bolus regimen in adults or children/ adolescents with type 1 diabetes. Studies in pregnancy, ob- servational studies, studies that compared premixed insulin or continuous subcutaneous insulin infusion/insulin pumps, and studies where the basal insulin was also changed were excluded. Only studies reporting baseline-endpoint change in insulin dose, or baseline and/or endpoint values, were included.

Results

Twenty-eight studies were identified (insulin glulisine, 4; insulin aspart, 7; insulin lispro, 17). Twenty- five studies compared a rapid-acting insulin analogue with regular human insulin, and 3 trials compared 2 rapid-acting insulin analogues. Overall, rapid-acting insulin analogues in a basal-bolus regimen provided similar or greater im- provements in glycemic control than regular human insulin at similar insulin doses, as well as a lower incidence of hypoglycemia.

Conclusions

Results of the studies identified in this literature review indicate that a basal-bolus regimen with prandial rapid-acting insulin analogue provides advan- tages over basal-bolus regimens using prandial regular hu- man insulin, providing improvements in glycemic control comparable to those obtained with regular human insulin, as well as a lower incidence of hypoglycemia. (Endocr Pract. 2010;16:486-505)

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.

REFERENCES (57)

  • L Monnier et al.

    Addition of rapid-acting insulin to basal insulin therapy in type 2 diabetes: Indications and modalities

    Diabetes Metab

    (2006)
  • P Raskin et al.

    A comparison of insulin lispro and buffered regular human insulin administered via continuous subcutaneous insulin infusion pump

    J Diabetes Complications

    (2001)
  • D Devendra et al.

    Type 1 diabetes: Recent developments

    BMJ

    (2004)
  • The Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications Research Group

    Retinopathy and nephropathy in patients with type 1 diabetes four years after a trial of intensive therapy

    N Engl J Med

    (2000)
  • DM Nathan et al.

    Intensive diabetes treatment and cardiovascular disease in patients with type 1 diabetes

    N Engl J Med

    (2005)
  • H Ulrich et al.

    Combining insulins for optimal blood glucose control in type I and 2 diabetes: Focus on insulin glulisine

    Vasc Health Risk Manag

    (2007)
  • SG Ashwell et al.

    Improved glycaemic control with insulin glargine plus insulin lispro: A multicentre, randomized, cross-over trial in people with type 1 diabetes

    Diabet Med

    (2006)
  • K Hermansen et al.

    Insulin analogues (insulin detemir and insulin aspart) versus traditional human insulins (NPH insulin and regular human insulin) in basal-bolus therapy for patients with type 1 diabetes

    Diabetologia

    (2004)
  • SG Ashwell et al.

    Treatment satisfaction and quality of life with insulin glargine plus insulin lispro compared with NPH insulin plus unmodified human insulin in people with type 1 diabetes

    Diabetes Care

    (2008)
  • A Siebenhofer et al.

    Short acting insulin analogues versus regular human insulin in patients with diabetes mellitus

    Cochrane Database Syst Rev

    (2006)
  • A Philotheou et al.

    Efficacy and safety of insulin glulisine versus insulin lispro as part of a basal-bolus insulin regimen in children and adolescents with type 1 diabetes mellitus

    Diabetologia

    (2008)
  • J Ludvigsson et al.

    Treatment with insulin aspart versus human insulin in children and adolescents with newly diagnosed type 1 diabetes

    Diabetologia

    (2007)
  • Brunetti P, Muggeo M, Cattin L, et al. Incidence of severe nocturnal hypoglycemia in patients with type 1 diabetes...
  • R Kawamori et al.

    Efficacy and safety of insulin glulisine in Japanese patients with type 1 diabetes mellitus

    Diabetes Obes Metab

    (2009)
  • SR Heller et al.

    Hypoglycaemia with insulin aspart: A double-blind, randomised, crossover trial in subjects with type 1 diabetes

    Diabet Med

    (2004)
  • PD Home et al.

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

    Diabet Med

    (2000)
  • P Raskin et al.

    Use of insulin aspart, a fast-acting insulin analog, as the mealtime insulin in the management of patients with type 1 diabetes

    Diabetes Care

    (2000)
  • M Dreyer et al.

    Efficacy and safety of insulin glulisine in patients with type 1 diabetes

    Horm Metab Res

    (2005)
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