Steady‐state pharmacokinetics and glucodynamics of the novel, long‐acting basal insulin LY2605541 dosed once‐daily in patients with type 2 diabetes mellitus

Abstract

In this Phase I study of fixed LY2605541 doses without titration, LY2605541 was well-tolerated and demonstrated a flat PK and GD profile accompanied by glucose normalization, prandial insulin dose reduction and no severe hypoglycaemia.

Hypoglycemia with New Generation Basal Analog Insulins: A Descriptive Critical Review

“…Data from patients with T2DM suggest that a relatively long time is required to achieve steady state: 7-10 days versus 2-4 days for IDeg and Gla-300, respectively [27,29]. BIL has a terminal half-life of 45-76 hours and low peak-trough fluctuation [34]. In a recent PK/PD study in patients with T2DM, the new insulin glargine LY2963016 was shown to have a similar profile to Gla-100, with a duration of action of approximately 24 hours [35].…”

Development of new basal insulin peglispro (LY2605541) ends in a disappointing result

“…PEGylation is novel in the context of insulin but is a well-established strategy to improve therapeutic properties of proteins, as shown for interferon. In the phase I study, LY2605541 showed flat PK and PD profiles accompanied by glucose normalization, prandial insulin dose reduction, and no severe hypoglycemia [7]. In addition to the long and flat PK/PD profile, LY2605541 demonstrates preferential hepatic versus peripheral action relative to insulin glargine in healthy individuals [8].…”

New Long-Acting Basal Insulins: Does Benefit Outweigh Cost?

“…2), thereby increasing the hydrodynamic size of the insulin-PEG complex (1,3,4,15,20,21,(45)(46)(47)(48). PegLispro has an even lower binding affinity for both the insulin receptor and IGF-1 receptor than lispro and a lower mitogenic potency than human insulin (45,47,48).…”

“…2), thereby increasing the hydrodynamic size of the insulin-PEG complex (1,3,4,15,20,21,(45)(46)(47)(48). PegLispro has an even lower binding affinity for both the insulin receptor and IGF-1 receptor than lispro and a lower mitogenic potency than human insulin (45,47,48). It possesses a prolonged duration of action exceeding 36 h as a result of delayed absorption and reduced clearance, with a low intrasubject variability in glucose lowering and a lower and quite different tissue distribution compared with the other insulin preparations (45,47,48).…”

“…PegLispro has an even lower binding affinity for both the insulin receptor and IGF-1 receptor than lispro and a lower mitogenic potency than human insulin (45,47,48). It possesses a prolonged duration of action exceeding 36 h as a result of delayed absorption and reduced clearance, with a low intrasubject variability in glucose lowering and a lower and quite different tissue distribution compared with the other insulin preparations (45,47,48). Both animal and human studies suggested that PegLispro may have a preferential hepato-specific action on glucose metabolism compared with insulin glargine (49).…”