Randomized, double-blind clinical trial comparing basal insulin peglispro and insulin glargine, in combination with prandial insulin lispro, in patients with type 1 diabetes: IMAGINE 3.
To compare the efficacy and safety of basal insulin peglispro (BIL), which has a flat pharmacokinetic and pharmacodynamic profile and a long duration of action, with insulin glargine (GL) in patients with type 1 diabetes.



In this phase III, 52-week, blinded study, we randomized 1114 adults with type 1 diabetes in a 3 : 2 distribution to receive either BIL (n = 664) or GL (n = 450) at bedtime, with preprandial insulin lispro, using intensive insulin management. The primary objective was to compare glycated haemoglobin (HbA1c) in the groups at 52 weeks, with a non-inferiority margin of 0.4%.



At 52 weeks, mean (standard error) HbA1c was 7.38 (0.03)% with BIL and 7.61 (0.04)% with GL {difference -0.22% [95% confidence interval (CI) -0.32, -0.12]; p < 0.001}. At 52 weeks more BIL-treated patients reached HbA1c <7% (35% vs 26%; p < 0.001), the nocturnal hypoglycaemia rate was 47% lower (p < 0.001) and the total hypoglycaemia rate was 11% higher (p = 0.002) than in GL-treated patients, and there was no difference in severe hypoglycaemia rate. Patients receiving BIL lost weight, while those receiving GL gained weight [difference -1.8 kg (95% CI -2.3, -1.3); p < 0.001]. Treatment with BIL compared with GL at 52 weeks was associated with greater increases from baseline in levels of serum triglyceride [difference 0.19 mmol/l (95% CI 0.11, 0.26); p < 0.001] and alanine aminotransferase (ALT) levels [difference 6.5 IU/l (95% CI 4.1, 8.9), p < 0.001], and more frequent injection site reactions.



In patients with type 1 diabetes, treatment with BIL compared with GL for 52 weeks resulted in a lower HbA1c, more patients with HbA1c levels <7%, and reduced nocturnal hypoglycaemia, but more total hypoglycaemia and injection site reactions and higher triglyceride and ALT levels.
International Diabetes Center, Minneapolis, MN, USA.
R M
RM
Bergenstal
Christchurch Hospital Diabetes Center, Christchurch, New Zealand.
H
H
Lunt
Mossakowski Clinical Research Centre, Polish Academy of Science, Warsaw, Poland.
E
E
Franek
Hopital Bichat Claude Bernard, Paris, France.
F
F
Travert
Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN, USA.
J
J
Mou
Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN, USA.
Y
Y
Qu
Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN, USA.
C J
CJ
Antalis
Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN, USA.
M L
ML
Hartman
Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN, USA.
M
M
Rosilio
Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN, USA.
S J
SJ
Jacober
Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN, USA. ebastyr@comcast.net.|Indiana University School of Medicine, Indianapolis, IN, USA. ebastyr@comcast.net.
E J
EJ
Bastyr
D000328:Adult; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000188:drug therapy*; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D006442:Glycated Hemoglobin / Q000032:analysis / Q000187:drug effects; D006801:Humans; D000069036:Insulin Glargine / Q000008:administration & dosage* / Q000009:adverse effects; D061268:Insulin Lispro / Q000008:administration & dosage* / Q000009:adverse effects / Q000031:analogs & derivatives*; D008297:Male; D062407:Meals; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000008:administration & dosage* / Q000009:adverse effects
D001786:Blood Glucose; D006442:Glycated Hemoglobin; D000069036:Insulin Glargine; D061268:Insulin Lispro; D011092:Polyethylene Glycols; C000621851:basal insulin peglispro
basal insulin; glycaemic control; hypoglycaemia; randomized trial; type 1 diabetes