The past, present, and future of basal insulins

Abstract

Insulin production by the pancreas follows a basic pattern where basal levels of insulin are secreted during fasting periods, with prandial increases in insulin associated with food ingestion. The aim of insulin therapy in patients with diabetes is to match the endogenous pattern of insulin secretion as closely as possible without causing hypoglycaemia. There are several optimal pharmacokinetic and pharmacodynamic properties of long-acting basal insulins that can help to achieve this aim, namely, as follows: activity that is flat and as free of peaks as possible, a duration of action of ≥24-h, and as little day-to-day variation as possible. The long-acting basal insulins are a fundamental therapy for patients with type 1 and type 2 diabetes, and those that are currently available have many benefits; however, the development of even longer-acting insulins and improved insulin delivery techniques may lead to better glycemic control for patients in the future. Established long-acting basal insulins available in the United States and Europe include insulin glargine 100 units/mL and insulin detemir, both of which exhibit similar glycemic control to that of the intermediate-acting neutral protamine Hagedorn insulin, but with a reduction in hypoglycaemia. Newer insulin products available include new insulin glargine 300 units/mL (United States and Europe) and the ultra-long-acting insulin degludec (Europe) with basal insulin peglispro currently in development. These new insulins demonstrate different pharmacokinetic/pharmacodynamic profiles and longer durations of action (>24 h) compared with insulin glargine 100 units/mL, which may lead to potential benefits. The introduction of biosimilar insulins may also broaden access to insulins by reducing treatment costs. Copyright © 2015 John Wiley & Sons, Ltd.

Efficacy and Safety of Biosimilar Insulins Compared to Their Reference Products: A Systematic Review

“…While the European Medicine Agency (EMA) and US FDA have stringent regulations and assessments for comparability between biosimilar and its originator products [47][48][49][50], many other countries do not have the same regulations. Several biosimilar insulins, such as Bonglixan (Mexico), Glaritus (India), Wosulin(India) and Gensulin(India), are currently available in the marketplace, yet have not been subject to rigorous scientific scrutiny and regulatory evaluation [10,24,[51][52][53]. Such data will continue to be of high interest to patients, providers and payers alike, given the inevitability of continued questions and debates about the appropriate role of biosimilar insulins and other biosimilar products in clinical practice [54,55].…”

Evaluation of Safety and Efficacy of Glaritus<sup>®</sup> versus Lantus<sup>®</sup> in Combination with Insulin Lispro among Adults with Type 1 Diabetes Mellitus-Phase IV Study

“…These new insulins have comparatively different pharmacokinetic/pharmacodynamic profiles and demonstrate longer durations of action (>24 h) compared with insulin glargine 100 units/mL, which may lead to potential benefits. Hence, the launch of biosimilar insulins may also widen the access to insulins by reducing treatment costs [14].…”

“…These LAIA achieve consistent glycemic control for a longer period of time ruling out the need for multiple dosing [10]. However, the development of even longer-acting insulins and improved insulin delivery techniques may lead to better glycemic control for patients in the future [14].…”

Clinical value of glargine 300 U/mL based on randomized trials and routine medical practice

“…Mechanism of prolonged activity of glargine, irrespective of its concentration, involves precipitation in neutral pH of the subcutaneous tissue and formation of a compact depot [1]. Due to 3 × higher concentration, a volume of Gla-300 injection is by 2/3 lower than that of Gla-100.…”