Elsevier

Endocrine Practice

Volume 18, Issue 3, May–June 2012, Pages 418-424
Endocrine Practice

Review Article
Continuous Subcutaneous Infusion of Insulin Lispro in Children and Adolescents with Type 1 Diabetes Mellitus

https://doi.org/10.4158/EP11265.RAGet rights and content

ABSTRACT

Objective

To provide a comprehensive review of insulin lispro administered by continuous subcutaneous insulin infusion (CSII) in children and adolescents.

Methods

We performed PubMed literature searches to identify clinical studies of insulin lispro administered via CSII within pediatric and adolescent populations.

Results

Twenty-six studies involving 2521 pediatric patients with type 1 diabetes mellitus met inclusion criteria. Of these, 10 were randomized controlled trials (RCTs), 6 of which compared insulin lispro CSII with multiple daily injection (MDI) therapy. We identified 7 additional prospective, nonrandomized studies and 9 retrospective studies. Within the RCTs, endpoint hemoglobin A1c levels ranged from 6.3% to 8.5% for insulin lispro CSII therapy and from 6.2% to 8.7% for those trials with MDI comparator arms. In those trials that compared insulin lispro CSII with MDI, the endpoint hemoglobin A1c achieved with insulin lispro was similar or improved compared with observations in the MDI treatment arm. In the RCTs, severe hypoglycemia rates of 0.1 to 0.3 episodes/patient per year were reported for insulin lispro CSII therapy; those trials with MDI comparator arms reported relatively similar severe hypoglycemia rates (0.1 to 0.5 episodes/patient per year). Events of diabetic ketoacidosis (DKA) were rare. Where reported, insulin lispro CSII and MDI therapy demonstrated a similar occurrence of DKA and incidence of severe hypoglycemia. Prospective and retrospective studies demonstrated results similar to the RCT findings.

Conclusions

In 26 studies of more than 2500 pediatric and adolescent patients with type 1 diabetes, with more than 1000 patients specifically receiving insulin lispro CSII, insulin lispro CSII therapy consistently demonstrated similar or improved efficacy and safety vs studied comparators. (Endocr Pract. 2012;18:418-424)

Section snippets

INTRODUCTION

Intensive management of diabetes delays the onset and progression of microvascular and cardiovascular complications associated with type 1 diabetes mellitus (1,2).

Rapid-acting insulin analogues, with a faster absorption rate, an earlier and higher peak insulin concentration, and a shorter duration of action than regular human insulin (3,4), have more physiologic pharmacokinetic, and pharmacodynamic profiles that may facilitate intensive management of diabetes. Humalog (insulin lispro injection,

Literature Search Criteria

Literature searches were conducted in PubMed using the search terms “pediatric,” “adolescent,” “insulin,” “pump,” “insulin infusion,” “continuous subcutaneous insulin infusion (CSII),” and “lispro” to identify relevant studies. Studies were also obtained from references included in individual articles and review articles. Only articles that specifically mentioned lispro as the insulin used and that evaluated CSII in a clinical setting of a primary pediatric or adolescent population (defined as

RESULTS

Twenty-six studies met final inclusion criteria: 10 were randomized controlled trials (8., 9., 10., 11., 12., 13., 14., 15., 16., 17.) (RCTs); 7 were prospective, nonrandomized studies (18., 19., 20., 21., 22., 23., 24.); and 9 were retrospective studies (25., 26., 27., 28., 29., 30., 31., 32., 33.). A total of 2521 patients were enrolled in these studies: 526 in RCTs, 471 in prospective studies, and 1524 in retrospective studies. Based on this enrollment, in an RCT setting, 220 pediatric

DISCUSSION

Insulin lispro administered via CSII, vs studied comparators, consistently demonstrated similar or improved efficacy and safety in children and adolescents with type 1 diabetes. This review encompassed multiple RCTs, including prospective and retrospective studies, with comparators including other rapid-acting insulin analogues, MDI therapy, and prepump therapy periods, with more than 2500 pediatric patients evaluated in a formal study setting and more than 1000 patients specifically receiving

CONCLUSION

Despite the study’s limitations, this clinical review of insulin lispro administered via CSII in pediatric and adolescent patients with type 1 diabetes demonstrates that CSII with insulin lispro compared with current alternatives provides similar or improved efficacy in conjunction with a similar or improved safety profile, as measured by incidence of severe hypoglycemia or DKA. As further therapeutic advancements in insulin formulations, insulin administration technologies, and monitoring

DISCLOSURE

Kevin Kaiserman, MD, is a paid consultant and speaker for Eli Lilly and Company and a paid consultant, researcher, and speaker for Medtronic. Henry Rodriguez, MD, is a paid consultant and speaker for Eli Lilly and Company. Amanda Stephenson, RN, and Jessie L. Fahrbach, MD, are full-time employees and minor stockholders of Lilly USA, LLC, and Eli Lilly and Company respectively. Linda Wolka, BS, MT(ASCP)SH, is a retired employee of Lilly USA, LLC.

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