A Critical Appraisal of the Role of Insulin Analogues in the Management of Diabetes Mellitus

Abstract

Insulin is one of the oldest and best studied treatments for diabetes mellitus. Despite many improvements in the management of diabetes, the nonphysiological time-action profiles of conventional insulins remain a significant obstacle. However, the advent of recombinant DNA technology made it possible to overcome these limitations in the time-action profiles of conventional insulins. Used as prandial (e.g. insulin lispro or insulin aspart) and basal (e.g. insulin glargine) insulin, the analogues simulate physiological insulin profiles more closely than the older conventional insulins. If rapid-acting insulin analogues are used in the hospital, healthcare providers will need a new mind-set. Any error in coordination between timing of rapid-acting insulin administration and meal ingestion may result in hypoglycaemia. However, guidelines regarding in-hospital use of insulin analogues are few. The safety profile of insulin analogues is still not completely established in long-term clinical studies. Several studies have shown conflicting results with respect to the tumourigenic potential of this new class of agents. The clinical implications of these findings are not clear. Although novel insulin analogues are promising 'designer drugs' in our armamentarium to overcome some of the limitations of conventional insulin therapy, cost may be a limiting factor for some patients.

Allergy reactions to insulin: effects of continuous subcutaneous insulin infusion and insulin analogues

“…The human insulin analogues lispro and aspart are produced by interchange of the positions of the amino acids B28-Pro and B29-Lys, and replacing B28-Pro with Asp, respectively. These changes cause rapid dissociation of hexamers into monomers spontaneously, resulting in rapid absorption, action, and degradation of insulin [5,6]. Ideally, insulin analogues should neither produce an immune response that results in local or systemic allergic manifestations in excess of those of human insulin preparations nor generate antibodies that bind to and neutralize insulin.…”

“…New long-acting insulin analogues such as insulin glargine and insulin detemir offer the potential advantage of a better basal insulin coverage over a 24-h period as compared to insulin NPH, with less hypoglycaemic events [5,6]. Therefore, once-daily dose of insulin glargine has been proposed as an alternative to CSII as it provides more effective glycaemic control over 24 hours as compared to intermediate insulin NPH [21,22].…”

“…Recent data showed that CSII with short-acting insulin analogues (insulin lispro, insulin aspart) provides better control of postprandial hyperglycaemia and further reduced risk of hypoglycaemia, leading to a significant improvement in glycated haemoglobin (HbA1c) and quality of life [3,4]. Therefore, short-acting insulin analogues are now considered as the first choice for CSII therapy [5,6]. In addition, this approach may offer new possibilities in the management of allergy to human insulin.…”

New Therapeutic Approaches in Type 2 Diabetes

“…Therefore, the pharmaceutical companies successfully developed analogues of insulin, by modifying some amino acids in the sequence of insulin molecule. This led to the launch of ultra-short acting insulin analogues (aspart, glulisine, lispro), on one hand, and of basal insulin analogues (glargine, detemir), on the other (11). As compared to classical insulin formulations, these new insulin analogues do not necessarily improve overall glucose control (as assessed by Hb1A1c levels), but are associated with better prandial glucose control, lower risk of (nocturnal) hypoglycaemia, better reproducibility of fasting glycaemia and/or slightly lower weight gain (11).…”

“…This led to the launch of ultra-short acting insulin analogues (aspart, glulisine, lispro), on one hand, and of basal insulin analogues (glargine, detemir), on the other (11). As compared to classical insulin formulations, these new insulin analogues do not necessarily improve overall glucose control (as assessed by Hb1A1c levels), but are associated with better prandial glucose control, lower risk of (nocturnal) hypoglycaemia, better reproducibility of fasting glycaemia and/or slightly lower weight gain (11). As classical insulin formulations, these new insulin analogues can be injected once a day as add-on basal insulin therapy to oral agents, twice (or threefold) daily with the use of premixed insulin formulations or four times daily when a basal-prandial insulin regimen is selected.…”