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. K E Y W O R D Sbasal insulin, drug development, drug mechanism, hypoglycaemia, insulin therapy Insulin therapy has long been a mainstay of therapy for type 1 and

Non‐alcoholic fatty liver disease (NAFLD) prevalence and its metabolic associations in patients with type 1 diabetes and type 2 diabetes

“…The aim of this investigation was to assess the prevalence and clinical phenotype of NAFLD in patients with T1D and T2D. Data are derived from patients who had LFC evaluated by MRI in four phase 3 studies from the basal insulin peglispro (BIL) IMAGINE development programme …”

The effects of basal insulin peglispro vs. insulin glargine on lipoprotein particles by NMR and liver fat content by MRI in patients with diabetes

“…The strengths of this study include the carefully characterized subgroup of patients from a large Phase 3 program in which three cohorts of patients with different diabetes types were studied [5]. There was uniform collection of serial lipid profiles and LFC, measures of glycemic efficacy, insulin dosing and adverse event profiles.…”

“…Basal insulin peglispro (BIL) is a novel long-acting insulin analog with a large hydrodynamic size [3] and hepato-preferential action due to reduced peripheral effect [4, 5]. This reduced peripheral effect on glucose disposal suggests a reduced effect on lipogenesis; increased lipolysis in insulin-treated patients who were changed to BIL likely contributed to the observed lipid changes.…”

Cytokeratin-18 and Enhanced Liver Fibrosis Scores in Type 1 and Type 2 Diabetes and Effects of Two Different Insulins

“…These patients are a cohort from the phase III BIL development program 27. LFC and liver enzyme data for this cohort have been published 7 28.…”