Insulin analogues: have they changed insulin treatment and improved glycaemic control?

Abstract

To improve insulin therapy, new insulin analogues have been developed. Two fast-acting analogues with a more rapid onset of effect and a shorter duration of action combined with a low day-to-day variation in absorption rate are now available. Despite this favourable time-action profile most studies have not been able to show any improvement in overall glycaemic control with the fast-acting analogues. A reduced post-prandial increase in blood glucose has been found in all studies, whereas between 3 and 5 h after the meal and during the night an increased blood glucose level is the normal course. This is probably the main explanation for the absence of improvement in overall glycaemic control when compared with regular human insulin. A tendency to a reduction in hypoglycaemic events during treatment with fast-acting analogues has been observed in most studies. Recent studies have indicated that NPH insulin administered several times daily at mealtimes can improve glycaemic control without increasing the risk of hypoglycaemia. The fast-acting analogues are now also available as insulin mixed with NPH. Insulin glargine is a new long-acting insulin which is soluble and precipitates after injection, resulting in a long half-life with a residual activity of about 50% 24 h after injection. Insulin glargine is a peakless insulin and studies in both type 1 and type 2 diabetic patients indicate that glargine improves fasting blood glucose control and reduces the incidence of nocturnal hypoglycaemia. Surprisingly, the new fast-acting analogues have not achieved the expected commercial success, which emphasises the need for new strategies for basal insulin supplementation, exercise, diet and blood glucose monitoring.

Insulin analogues (insulin detemir and insulin aspart) versus traditional human insulins (NPH insulin and regular human insulin) in basal-bolus therapy for patients with Type 1 diabetes

“…Recent basal-bolus trials with rapid-acting insulin analogues and NPH have shown significant improvements in postprandial glucose control [9,10,20], but these improvements only translated into small improvements in HbA 1 c. This suggested that optimisation of the basal insulin supply by the use of basal insulin analogues could lead to further improvements in glycaemic control [21,22]. In the current trial and earlier studies, insulin detemir has been shown to have a smooth time-action profile, meeting patients' basal insulin requirements [13,14].…”

Targeting postprandial hyperglycemia

“…As a result, these rapid-acting insulin analogues can be used aggressively at the time of a meal to promote disposal of postprandial glucose [283,284,286]. In patients with type 1 and type 2 diabetes mellitus, these insulins reduce postprandial hyperglycemia faster and more effectively than regular human insulin [281,[284][285][286]. All of the new semisynthetic rapid-acting insulins have a lower incidence of nocturnal hypoglycemia than regular human insulin with improved glycemic control in type 1 and type 2 diabetic patients [289][290][291][292][293][294][295][296][297].…”

“…Basal insulin treatment has very little effect on postprandial glucose levels, and, therefore, the use of short-acting insulins at mealtime is indicated to directly target postprandial hyperglycemia in both type 1 and type 2 diabetes mellitus. Several semisynthetic insulin analogues now exist with more rapid absorption and disappearance kinetics than regular human insulin [278][279][280][281]. These include lispro insulin, aspart insulin, and glulisine insulin.…”

Sustained-release self-dissolving micropiles for percutaneous absorption of insulin in mice

“…This study is the first trial to use porous silicate adsorbents as a pharmaceutical additive for percutaneous preparation. To obtain a long-acting sc insulin injection preparation, microcrystal suspension technology (Kwon et al 2004), PEGylation (Hinds et al 2005) and insulin analog (Madsbad 2002;Park et al 2005) are used. However, sc injection preparation cannot delete the pain from the patients.…”