Concentrated insulins: the new basal insulins

Abstract

IntroductionInsulin therapy plays a critical role in the treatment of type 1 and type 2 diabetes mellitus. However, there is still a need to find basal insulins with 24-hour coverage and reduced risk of hypoglycemia. Additionally, with increasing obesity and insulin resistance, the ability to provide clinically necessary high doses of insulin at low volume is also needed.Areas coveredThis review highlights the published reports of the pharmacokinetic (PK) and glucodynamic properties of concentrated insulins: Humulin-R U500, insulin degludec U200, and insulin glargine U300, describes the clinical efficacy, risk of hypoglycemic, and metabolic changes observed, and finally, discusses observations about the complexity of introducing a new generation of concentrated insulins to the therapeutic market.ConclusionHumulin-R U500 has a similar onset but longer duration of action compared with U100 regular insulin. Insulin glargine U300 has differential PK/pharmacodynamic effects when compared with insulin glargine U100. In noninferiority studies, glycemic control with degludec U200 and glargine U300 is similar to insulin glargine U100 and nocturnal hypoglycemia is reduced. Concentrated formulations appear to behave as separate molecular entities when compared with earlier U100 insulin analog compounds. In the review of available published data, newer concentrated basal insulins may offer an advantage in terms of reduced intraindividual variability as well as reducing the injection burden in individuals requiring high-dose and large volume insulin therapy. Understanding the PK and pharmacodynamic properties of this new generation of insulins is critical to safe dosing, dispensing, and administration.

Factors Affecting the Absorption of Subcutaneously Administered Insulin: Effect on Variability

“…Conversely, an increased depot concentration delays absorption and reduces the maximum plasma concentration, C max [ 18 ]. This applies for the human insulin 500 U formulation that is associated with a reduced C max and prolonged exposure, thus providing both prandial and basal coverage [ 100 , 101 ].…”

“…Besides a prolonged pharmacokinetic profile associated with use of some concentrated insulin preparations, their use also reduces the injection volume necessary, which in particular favours their use in highly insulin-resistant patients requiring high doses of insulin [ 100 , 105 , 106 ].…”

Nocturnal Glycemic Control with New Insulin Glargine 300 U/mL

“…Gla-300 is a new long-acting insulin product delivering the same unit amount of insulin glargine in one-third of the volume compared to Gla-100 and provides even greater glycemic control and hypoglycemia-reducing effects than Gla-100 through better mimicry of the physiological profile of endogenous basal insulin secretion during periods of fasting, between meals, and sleep [7–9]. In studies comparing the pharmacokinetic/pharmacodynamic (PK/PD) characteristics between Gla-100 and Gla-300, at equivalent doses, Gla-300 is demonstrated to consistently produce flatter, more evenly distributed and sustained insulin concentration and plasma glucose concentration-time curves than Gla-100 [10, 11].…”

Special aspects of concentrated insulins: basic characteristics and research findings

“…Появление в клинической практике высококонцентрированных инсулинов приводит к вопросам относительно преимуществ их использования у пациентов с СД, выбора подходящей группы пациентов и др. [4][5][6][7].…”