A randomized clinical trial comparing basal insulin peglispro and insulin glargine, in combination with prandial insulin lispro, in patients with type 1 diabetes: IMAGINE 1

Abstract

Aims: The primary objective was to demonstrate that basal insulin peglispro (BIL) was noninferior compared with insulin glargine (GL) for haemoglobin A1c (HbA1c) at 26 weeks with a non-inferiority margin of 0.4%. Results: At 26 weeks, mean HbA1c was 7.06% AE 0.04% and 7.43% AE 0.06% for patients assigned to BIL (N = 295) and GL (N = 160), respectively (difference -0.37% [95% CI: −0.50 to −0.23], P < .001); more patients on BIL achieved HbA1c <7% (44.9% vs 27.5%, P < .001). Compared with GL, patients using BIL lost weight, with lower fasting serum glucose and betweenday fasting blood glucose variability, and 36% less nocturnal hypoglycemia, 29% more total hypoglycemia and more severe hypoglycemia. Total and prandial insulin doses were lower with BIL; basal insulin doses were higher. Alanine aminotransferase increased with BIL, with more patients having elevations ≥3 × ULN. BIL treatment was associated with more frequent injection site reactions and an increase from baseline in serum triglycerides. Conclusions:In patients with type 1 diabetes, treatment with BIL compared to GL for 26 weeks was associated with lower HbA1c, less nocturnal hypoglycemia, lower glucose variability and weight loss. Increases in total and severe hypoglycemia, triglycerides, aminotransferases and injection site reactions were also noted. K E Y W O R D Sbasal insulin, glycaemic control, hypoglycaemia, randomised trial, type 1 diabetes

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

“…In this study, LS mean HbA1c after 12 weeks (6.8%) and 36 weeks (7.0%) of therapy is comparable to the BIL‐treated patients in other T1D trials: 7.1% and 7.4%, respectively, at 26 and 78 weeks in IMAGINE 1 ( n = 295) and 7.4% at 52 weeks in IMAGINE 3 ( n = 664) . Finally, the observations of the lipid changes and increases in ALT and AST in this study are consistent with changes observed in studies of comparing BIL to conventional insulins in patients previously treated with insulin . Each of these variables returned to baseline or near baseline during the 4 weeks off study drug in this and previous studies …”

“…These data are consistent with what would be expected of the long half‐life observed for BIL in PK studies . Furthermore, in other studies, glycaemic variability was lower with BIL than with comparator insulins (insulin glargine and NPH) . Reduction of glycaemic variability may not only allow more effective titration of basal insulin and improved glycaemic efficacy compared to insulin glargine or NPH but may also reduce nocturnal hypoglycaemia and perhaps reduce the risk or delay the onset of long‐term health concerns .…”

“…Limitations of this study include lack of comparator insulin for both efficacy and safety concerns and comparatively short durations of treatment for the primary analyses. These limitations are mitigated by the extensive data from other BIL trials with durations of 26‐78 weeks in which greater glycaemic efficacy was demonstrated in six comparator trials, including two in T1D, with an insulin glargine comparator . In this study, LS mean HbA1c after 12 weeks (6.8%) and 36 weeks (7.0%) of therapy is comparable to the BIL‐treated patients in other T1D trials: 7.1% and 7.4%, respectively, at 26 and 78 weeks in IMAGINE 1 ( n = 295) and 7.4% at 52 weeks in IMAGINE 3 ( n = 664) .…”

“…Furthermore, in other studies, glycaemic variability was lower with BIL than with comparator insulins (insulin glargine and NPH) . Reduction of glycaemic variability may not only allow more effective titration of basal insulin and improved glycaemic efficacy compared to insulin glargine or NPH but may also reduce nocturnal hypoglycaemia and perhaps reduce the risk or delay the onset of long‐term health concerns . Of note, the study cohort was comprised of T1D patients with a mean duration of diabetes of 20 years in whom more than half achieved an HbA1c of less than 7% after 12 weeks of therapy (lead‐in period) and for most patients this was maintained for the next 24 weeks.…”

“…BIL is a novel insulin with a half‐life greater than 24 hours as determined by pharmacokinetic/pharmacodynamics (PK/PD) studies . Moreover, Phase 2 and 3 clinical trials have demonstrated that there is less glycaemic variability during treatment with BIL, compared to treatment with glargine or isophane insulin (NPH) …”