title: Basal insulin peglispro: Overview of a novel long-acting insulin with reduced peripheral effect resulting in a hepato-preferential action.
abstract: Basal insulin peglispro (BIL) is a novel basal insulin with a flat, prolonged activity profile. BIL has been demonstrated in a dog model, in healthy men and in patients with type 1 diabetes (T1D) to have significant hepato-preferential action resulting from reduced peripheral activity. In the IMAGINE-Phase 3 clinical trial program, more than 6000 patients were included, of whom ~3900 received BIL. Of the 7 pivotal IMAGINE trials, 3 studies were double-blinded and 3 were in T1D patients. BIL consistently demonstrated a greater HbA1c reduction, less glycaemic variability and a clinically relevant reduction in the rates of nocturnal hypoglycaemia across comparator [glargine and isophane insulin (NPH)] studies. Trials using basal/bolus regimens had higher rates of total hypoglycaemia with BIL due to higher rates of daytime hypoglycaemia. Severe hypoglycaemia rates were similar to comparator among both patients with T1D or type 2 diabetes (T2D). T1D patients lost weight compared with glargine (GL). Patients with T2D tended to gain less weight with BIL than with glargine. Compared to glargine, BIL was associated with higher liver fat, triglycerides and alanine aminotransferase (ALT) levels, including a higher frequency of elevation of ALT ≥3 times the upper limit of normal, but without severe, acute drug-induced liver injury. Injection site reactions, primarily lipohypertrophy, were more frequent with BIL. In conclusion, BIL demonstrated better glycaemic control with reduced glucose variability and nocturnal hypoglycaemia but higher triglycerides, ALT and liver fat relative to conventional comparator insulin. The hepato-preferential action of BIL with reduced peripheral activity may account for these findings.
authors.affiliation: Eli Lilly and Company, Indianapolis, Indiana. jacober_scott_j@lilly.com.
authors.forename: S J
authors.initials: SJ
authors.lastname: Jacober
authors.affiliation: Eli Lilly and Company, Indianapolis, Indiana.
authors.forename: M J
authors.initials: MJ
authors.lastname: Prince
authors.affiliation: Eli Lilly and Company, Indianapolis, Indiana.
authors.forename: J M
authors.initials: JM
authors.lastname: Beals
authors.affiliation: Eli Lilly and Company, Indianapolis, Indiana.
authors.forename: M L
authors.initials: ML
authors.lastname: Hartman
authors.affiliation: Eli Lilly and Company, Indianapolis, Indiana.
authors.forename: Y
authors.initials: Y
authors.lastname: Qu
authors.affiliation: Eli Lilly and Company, Indianapolis, Indiana.
authors.forename: H
authors.initials: H
authors.lastname: Linnebjerg
authors.affiliation: Eli Lilly and Company, Indianapolis, Indiana.
authors.forename: P
authors.initials: P
authors.lastname: Garhyan
authors.affiliation: Eli Lilly and Company, Indianapolis, Indiana.
authors.forename: A
authors.initials: A
authors.lastname: Haupt
mesh_terms: D000410:Alanine Transaminase / Q000378:metabolism; D001786:Blood Glucose / Q000378:metabolism; D017322:Clinical Trials, Phase II as Topic; D017326:Clinical Trials, Phase III as Topic; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy* / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000378:metabolism; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007003:Hypoglycemia / Q000139:chemically induced; D007004:Hypoglycemic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D007328:Insulin / Q000627:therapeutic use; D000069036:Insulin Glargine / Q000627:therapeutic use; D061268:Insulin Lispro / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D007336:Insulin, Isophane / Q000627:therapeutic use; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D011092:Polyethylene Glycols / Q000494:pharmacology / Q000627:therapeutic use*; D016896:Treatment Outcome; D014280:Triglycerides / Q000378:metabolism; D015431:Weight Loss
chemical_list: D000410:Alanine Transaminase; D001786:Blood Glucose; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007328:Insulin; D000069036:Insulin Glargine; D061268:Insulin Lispro; D007336:Insulin, Isophane; D011092:Polyethylene Glycols; D014280:Triglycerides; C000621851:basal insulin peglispro; C517652:hemoglobin A1c protein, human
keywords: basal insulin; drug development; drug mechanism; hypoglycaemia; insulin therapy