Original ArticleBasal Insulin Degludec and Glycemic Control Compared to Aspart Via Insulin Pump in Type 1 Diabetes (BIGLEAP): A Single-Center, Open-Label, Randomized, Crossover Trial
Introduction
Continuous subcutaneous insulin infusion (CSII) has become the “gold standard” for the management of type 1 diabetes. Clinical trials have demonstrated that CSII, compared with multiple daily insulin injections (MDI), improves glycemic control; may reduce the incidence of hypoglycemia; and improves patient satisfaction and quality of life.1, 2, 3 These trials compared MDI regimens using neutral protamine Hagedorn or first-generation basal insulin analogs with CSII. Insulin degludec (IDeg) is a second-generation ultralong-acting insulin analog with a flat, stable glucodynamic profile and a duration of action of >42 hours.4 In glucose clamp studies and across multiple clinical trials, IDeg has demonstrated lower intraindividual between-day variability and less hypoglycemia than insulin glargine U100 in type 1 and type 2 diabetes.5 To date, no study has compared CSII with MDI with IDeg. The purpose of this prospective, randomized crossover trial was to compare glycemic control assessed by continuous glucose monitoring (CGM) between 2 methods of basal insulin delivery: either a single daily injection of IDeg, or CSII with insulin aspart in people with type 1 diabetes with optimized glycemic control using open-loop CSII and CGM. Bolus insulin was delivered via pump in both treatment groups to isolate and compare basal insulin effects independent of bolus insulin delivery method.
Section snippets
Study Design and Patients
The BIGLEAP trial was a phase 4, single-center, open-label, randomized crossover-controlled, proof-of-concept trial of patients with well-controlled type 1 diabetes conducted at Mountain Diabetes and Endocrine Center, an outpatient private endocrinology practice and research center. A 2-period crossover trial design was chosen to best allow treatment comparisons in a specific study population (ie, device-experienced individuals with good baseline glycemic control). In a crossover trial,
Results
Fifty-nine patients were screened for eligibility, of whom 53 were randomized. Participants were randomly assigned to 1 of 2 treatment sequences: 25 patients were assigned to a single daily injection of IDeg with bolus insulin aspart administered via pump, and 28 patients were assigned to their usual CSII regimen, each for a 20-week treatment period. Each group then crossed over to the other treatment for a second 20-week period. Five patients withdrew prior to randomization, and 1 patient
Discussion
To the authors knowledge, the BIGLEAP trial is the first trial comparing IDeg as basal insulin in combination with bolus insulin aspart to open-loop CSII aspart via pump in patients with well-controlled type 1 diabetes in combination with CGM. This trial found that IDeg provided similar 24-hour glycemic control compared with CSII aspart in terms of TIR and overall and nocturnal hypoglycemia.
This study was designed and powered to evaluate the superiority, rather than the noninferiority, of IDeg
Conclusion
In this crossover trial of patients with well-controlled type 1 diabetes using CSII and CGM, the substitution of IDeg for continuously infused insulin aspart for basal insulin delivery resulted in comparable glycemic control with equally low overall and nocturnal hypoglycemia. This study should improve the confidence of health care providers and patients that IDeg is an acceptable basal insulin alternative to basal insulin delivered via insulin pump should patients need to discontinue using
Acknowledgment
We thank the study patients and clinical research coordinators who carried out this trial. We dedicate this study with love and gratitude to the memories of Dr Vernon Hendrix, who contributed to the study design and to Benjamin Lane who performed the statistical analysis of the study data. This work was supported by Novo Nordisk, Baegsvard, Denmark. Novo Nordisk had no role in the study design, data collection, data analysis, data interpretation, or writing of the report.
Author Contributions
W.L. designed the trial
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