Similar HbA1c reduction and hypoglycaemia with variable- vs fixed-time dosing of basal insulin peglispro in type 1 diabetes: IMAGINE 7 study.

Abstract

AIMS:

To compare 24-hour fixed-time basal insulin peglispro (BIL) dosing with 8- to 40-hour variable-time BIL dosing for glycaemic control and safety in patients with type 1 diabetes. Primary outcome was non-inferiority of BIL variable-time dosing compared with fixed-time dosing for glycated haemoglobin (HbA1c) change after 12-week treatment (margin = 0.4%).

MATERIALS AND METHODS:

This Phase 3, open-label, randomized, cross-over study (N = 212) was conducted at 20 centres in the United States. During the 12-week lead-in phase, patients received BIL daily at fixed-times. Two 12-week randomized cross-over treatment phases followed, where patients received BIL dosed at either fixed- or variable-times. During the 4-week safety follow-up, patients received conventional insulins.

RESULTS:

During the lead-in period, least-squares mean HbA1c decreased from 7.5% to 6.8%. For BIL, variable-time dosing was non-inferior to fixed-time dosing for HbA1c change [least-squares mean difference = 0.06%, 95% confidence interval (-0.01, 0.13)]. In both regimens, HbA1c increased slightly during the cross-over periods, but remained significantly below baseline. Variable- and fixed-time dosing regimens had similar rates of total hypoglycaemia (10.4 ± 0.62 and 10.5 ± 0.67 events/patient/30 days, P = .947) and nocturnal hypoglycaemia (1.3 ± 0.11 and 1.5 ± 0.13 events/patient/30days, P = .060). Comparable proportions of patients achieved HbA1c < 7.0% with variable- [91 (54.5%)] and fixed-time dosing [101 (60.5%)].

CONCLUSIONS:

Treatment with BIL allows patients to use flexible dosing intervals from 8 to 40 hours. Glycaemic efficacy (HbA1c), glycaemic variability and hypoglycaemia are similar to fixed-time dosing, suggesting that BIL could potentially provide flexibility in dosing for patients who miss their daily basal insulin.

• Authors: S Garg, J-L Selam, A Bhargava, N Schloot, J Luo, Q Zhang, J G Jacobson, B J Hoogwerf
• Journal: Diabetes, obesity & metabolism (Diabetes Obes Metab) Vol. 18 Suppl 2 Pg. 43-49 (10 2016) ISSN: 1463-1326 [Electronic] England
• PMID: 27393722 (Publication Type: Clinical Trial, Phase III, Comparative Study, Journal Article, Randomized Controlled Trial)
• Copyright: © 2016 John Wiley & Sons Ltd.

Chemical References

• Blood Glucose
• Glycated Hemoglobin A
• Hypoglycemic Agents
• Insulin Lispro
• basal insulin peglispro
• hemoglobin A1c protein, human
• Polyethylene Glycols

Topics

• Adult
• Blood Glucose (metabolism)
• Cross-Over Studies
• Diabetes Mellitus, Type 1 (drug therapy, metabolism)
• Drug Administration Schedule
• Female
• Glycated Hemoglobin (metabolism)
• Humans
• Hypoglycemia (chemically induced)
• Hypoglycemic Agents (administration & dosage)
• Insulin Lispro (administration & dosage, analogs & derivatives)
• Least-Squares Analysis
• Male
• Middle Aged
• Polyethylene Glycols (administration & dosage)
• Treatment Outcome