The ongoing evolution of basal insulin therapy over 100 years and its promise for the future

Abstract

The evolution of basal insulin therapy over the past 100 years since the discovery of insulin is a testimony to the biomedical bench‐to‐bedside process, wherein incremental advances in the basic sciences are progressively translated over time into a series of enhancements in clinical care, each building upon the success of its predecessors. The emergence of recombinant DNA technology and the resultant biosynthesis of human insulin in the 1980s provided the critical capacity to bioengineer designer insulin analogues with pharmacokinetic and pharmacodynamic properties that can better mimic, although not fully replicate, the effects of endogenous insulin secretion. Through these efforts, basal insulin therapy has progressed over this time from first‐generation analogues (glargine U‐100, detemir) to second‐generation analogues (glargine U‐300, degludec) to ultra‐long‐acting formulations that are suitable for administration once weekly (icodec). Each iteration in this progression has represented a step closer towards the goal of replicating the continuous secretion of insulin that normally comprises the basal output of the pancreatic beta‐cells between meals, during episodes of fasting and overnight. However, it may be that we may have reached the achievable limit in the context of an “open‐loop” approach, such that only with the addition of closed loop control will we be able to achieve physiologic basal insulin replacement. In this review, we will examine the evolution of basal insulin therapy over the past 100 years and its implications for patient care and outcomes in current practice and the future.

Expert Opinion by Clinicians on the Use of Insulin Therapy in People with Hepatic Impairment

“…7 Progressive breakthroughs in the techniques for protraction or prolongation of insulin activity have spurred the growth of basal insulin therapy to establish this desired profile in patients. 36 Insulin should be initiated if the patients do not respond to OADs alone or in combination, or if they have hepatic failure. 37 When the blood glucose levels are >180 mg/dL or in critically ill people, basal or short-acting insulins could be used to overcome glucose fluctuations and improve glycemic levels.…”

“…39,40 Basal insulin therapy has progressed over time from first-generation analogs (glargine U-100, detemir) to second-generation analogs (glargine U-300, degludec) to ultra-long-acting formulations (icodec). 36 The Research Society for the Study of Diabetes in India-Endocrine Society of India Consensus Group recommends the use of rapid-acting insulin analogs (insulin aspart or lispro) to attain targeted glycemic levels with a low risk of hypoglycemia in T2DM individuals with hepatic impairment. 38 When compared to neutral protamine Hagedorn insulin or premixed insulins, evidence suggests that basal insulin analogs such glargine, detemir, and degludec are effective and safe, with a lower risk of hypoglycemia and weight gain.…”

Therapie des Typ-2-Diabetes

“…Eine umfangreiche Diskussion über neue Insuline würde jedoch den Rahmen dieser Praxisempfehlungen bei Weitem sprengen. Aber als Beitrag zu 100 Jahre Insulin wurden umfangreiche Reviews publiziert [275][276][277].…”

100 anos de insulina: como a descoberta do hormônio revolucionou o tratamento de diabetes tipo 1

“…Os análogos apresentam alterações na sua cadeia de aminoácidos, trazendo melhorias no seu tempo de ação. (Retnakaran et al, 2021).…”