title: Similar HbA1c reduction and hypoglycaemia with variable- vs fixed-time dosing of basal insulin peglispro in type 1 diabetes: IMAGINE 7 study.
abstract: 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%).
  
  
  
  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.
  
  
  
  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%)].
  
  
  
  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.affiliation: Barbara Davis Center for Diabetes, University of Colorado Denver, Aurora.
authors.forename: S
authors.initials: S
authors.lastname: Garg
authors.affiliation: Diabetes Research Center, Tustin, California.
authors.forename: J-L
authors.initials: JL
authors.lastname: Selam
authors.affiliation: Iowa Diabetes and Endocrinology Research Center, Des Moines, Iowa.
authors.forename: A
authors.initials: A
authors.lastname: Bhargava
authors.affiliation: Lilly Deutschland GmbH, Bad Homburg, Germany.
authors.forename: N
authors.initials: N
authors.lastname: Schloot
authors.affiliation: Eli Lilly and Company, Indianapolis, Indiana.
authors.forename: J
authors.initials: J
authors.lastname: Luo
authors.affiliation: Eli Lilly and Company, Indianapolis, Indiana.
authors.forename: Q
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Eli Lilly and Company, Indianapolis, Indiana.
authors.forename: J G
authors.initials: JG
authors.lastname: Jacobson
authors.affiliation: Eli Lilly and Company, Indianapolis, Indiana. hoogwerf_byron_james@lilly.com.
authors.forename: B J
authors.initials: BJ
authors.lastname: Hoogwerf
mesh_terms: D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D018592:Cross-Over Studies; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy* / Q000378:metabolism; D004334:Drug Administration Schedule; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007003:Hypoglycemia / Q000139:chemically induced*; D007004:Hypoglycemic Agents / Q000008:administration & dosage*; D061268:Insulin Lispro / Q000008:administration & dosage / Q000031:analogs & derivatives*; D016018:Least-Squares Analysis; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000008:administration & dosage*; D016896:Treatment Outcome
chemical_list: D001786:Blood Glucose; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D061268:Insulin Lispro; D011092:Polyethylene Glycols; C000621851:basal insulin peglispro; C517652:hemoglobin A1c protein, human
keywords: basal insulin peglispro; continuous glucose monitoring; variable-time dosing