A review of modern insulin analogue pharmacokinetic and pharmacodynamic profiles in type 2 diabetes: improvements and limitations

Abstract

Insulin analogues have been engineered to enhance desired molecular properties without altering immunogenicity. The majority of insulin pharmacology studies are conducted in healthy volunteers and patients with type 1 diabetes. At present, there are more patients with type 2 than type 1 diabetes receiving insulin treatment. As the responsibility for initiating insulin therapy in these patients continues to shift to primary care, it will be important for general practitioners to understand the different pharmacological properties of insulin preparations in patients with type 2 diabetes, so that treatment can be adapted to meet patients’ physiological and lifestyle requirements. The purpose of this review is to summarize pharmacological studies of insulin analogues in patients with type 2 diabetes. Faster onset of action of rapid acting insulin analogues has improved postprandial glycaemic control. Biphasic insulin analogues are associated with a lower incidence of nocturnal hypoglycaemia compared with human biphasic preparations and allow for intensification from once to twice or thrice daily dosing. More predictable glycaemic-lowering profiles of the insulin analogues have also led to reductions in nocturnal hypoglycaemia, particularly comparing long-acting insulin analogues with protaminated human insulin. Enhancing insulin self-association and reversible binding with albumin has led to further reductions in variability. However, improvements can still be made. Effective once daily clinical dosing of long-acting insulin analogues is not possible in all patients. In addition, the protaminated component of biphasic insulin analogues do not provide the duration of action or profile for physiological basal insulin replacement and neither insulin glargine nor insulin detemir are suitable for mixing with other insulin analogues as this would substantially alter their pharmacokinetic properties. Enhancing the pharmacological predictability and extending the duration of action could simplify insulin titration and further reduce the incidence of hypoglycaemia.

Glycemic Control in Pregnant Diabetic Woman: Comparison between Conventional Insulin and Analogs

“…The latter result could be explained on the one hand by a slightly higher frequency of type 1 diabetics in group 2 and on the other hand the indication of insulin analogues could have been Insulin analogues offer the opportunity to mimic the physiological secretion of insulin thus allowing more flexibility and freedom to patients and a lower risk of hypoglycaemia [19]. Insulin detemir disappears more slowly from the subcutaneous tissue than NPH and has a more "flat" pharmacodynamics than of NPH (no peak action at usual doses).…”

IDegAsp (insulin degludec + insulin aspart) for the management of type 2 diabetes: current status

“…The hypoglycemia risk of protamine-based premixes derives partly from pharmacological variability, resulting in hyper-and hypoinsulinemia [28]. There is, therefore, a strong clinical need for the development of a combination insulin that can provide sustained and stable basal insulin coverage together with optimal prandial insulin kinetics in a single injection, without either compromising the other.…”

“…The pharmacokinetic profile of the protamine-based basal component of existing biphasic insulins does not give a physiologically flat profile. In addition, existing biphasic insulins may not provide the duration of action for a physiological basal insulin replacement [27,28] and are more complex to titrate than basal insulin analogs used alone. Additional disadvantages include the fixed ratio of meal to basal insulin dose, and the inability of some basal insulin analogs (insulin detemir [IDet] and insulin glargine [IGlar]) to be co-formulated with mealtime insulin due to alterations of their pharmacokinetic/pharmacodynamic profiles, making them unsuitable for optimum glycemic control [29][30][31].…”

Role of insulin in management of type 2 diabetes mellitus

“…Biphasic insulin analogues have a mixture of rapid or short acting insulin analogue with intermediateacting insulin. 29 Table 1 shows Pharmacokinetic profiles of Insulin therapies.…”