The pharmacokinetics and pharmacodynamics of rapid‐acting insulin analogues and their clinical consequences

Abstract

Postprandial glucose excursions can inhibit achievement of good glycaemic control, and possibly have a specific effect on the risk of vascular comorbidities. Rapid-acting analogues control these excursions better than human insulin because their pharmacokinetic/pharmacodynamic (PK/PD) profile is closer to that of meal-time endogenous insulin secretion. Review of the findings of PK/PD studies and clinical trials suggests that the three marketed rapid-acting analogues--insulin lispro, insulin aspart and insulin glulisine--are equally efficacious and safe. In comparison with human insulin when using the same basal insulin, they provide comparable glycaemic control with a reduced risk of hypoglycaemia, although the combination of rapid-acting and basal analogues reduces glycated haemoglobin (HbA(1c)) more than human meal-time insulin combined with neutral protamine Hagedorn (NPH) insulin. Some studies have suggested that insulin glulisine has a slightly faster onset of action compared with insulin lispro or insulin aspart, but this has not been translated into demonstrable clinical benefit. Treatment satisfaction in patients with diabetes has been higher when therapy with a rapid-acting analogue is used instead of human insulin, perhaps due to differences in advised timing of injection. The largest benefits in efficacy, hypoglycaemia incidence, treatment satisfaction and quality of life have occurred when patients receive an all-analogue meal-time plus basal regimen as compared with an all-human insulin regimen. No new safety issues have been identified with the marketed rapid-acting analogues, and their insulin-like growth factor 1 receptor affinity and mitogenic activity are comparable to human insulin.

Update on newer antidiabetic drugs in clinical practice

“…The molecular structures of insulin lispro, insulin aspart and insulin glulisine, differ only slightly from human insulin, with two amino acid changes for insulin lispro and insulin glulisine and one for insulin aspart [2,3]. This allows them to be absorbed more quickly than unmodified (regular/soluble) human insulin [2].…”

“…The rapid acting insulin analogues have a PK profile similar to that of meal time insulin secretion and allows for better control of post meal blood glucose surges [2,3]. Compared to soluble/regular insulin (onset of action 30-60 minutes, duration of action 8-10 hours), the rapid-acting insulin analogues have a faster onset (5-15 minutes) and shorter duration (4-6 hours) of action [2].…”

Stellenwert der Insulinanaloga bei der Therapie von Menschen mit Typ-2-Diabetes

“…Dadurch tritt die Insulinwirkung innerhalb von 5-15 Minuten nach subkutaner Injektion ein, so dass in der Regel kein Spritz-Ess-Abstand notwendig ist [13]. Dies kann vorteilhaft sein, wenn der Zeitpunkt für eine Mahlzeit schwer vorhersehbar ist.…”

“…Die maximale Serumkonzentration der kurz wirksamen Insulinanaloga ist nach subkutaner Gabe deutlich höher und die Wirkungsdauer kürzer als bei kurz wirksamem Humaninsulin (q Abb.1) [13]. Dementsprechend zeigen kurz wirksame Insulinanaloga eine signifikant bessere postprandiale Glukoseregulation [13,21,30], bei gleichzeitig besserer Hemmung der Glukoseproduktion in der Leber [2].…”

“…Dementsprechend zeigen kurz wirksame Insulinanaloga eine signifikant bessere postprandiale Glukoseregulation [13,21,30], bei gleichzeitig besserer Hemmung der Glukoseproduktion in der Leber [2].…”