NovoRapid Mechanism of Action

insulin aspart


Novo Nordisk


Zuellig Pharma
Full Prescribing Info
Pharmacotherapeutic Group: Fast acting insulins and analogues, ATC Code: A10A B05.
Pharmacology: Pharmacodynamics: The blood glucose lowering effect of insulin occurs when the molecules facilitate the uptake of glucose by binding to insulin receptors on muscle and fat cells and simultaneously inhibit the output of glucose from the liver.
NovoRapid produces a more rapid onset of action compared to soluble human insulin, together with a lower glucose concentration, as assessed within the 1st 4 hrs after a meal. NovoRapid has a shorter duration of action compared to soluble human insulin after SC injection.
When NovoRapid is injected SC, the onset of action will occur within 10-20 min of injection. The maximum effect is exerted 1-3 hrs after injection. The duration of action is 3-5 hrs.
Adults: Clinical trials in patients with type 1 diabetes have demonstrated a lower postprandial blood glucose with NovoRapid compared to soluble human insulin. In 2 long-term open label trials in patients with type 1 diabetes comprising 1070 and 884 patients, respectively, NovoRapid reduced glycosylated haemoglobin by 0.12 (95% C.I. 0.03; 0.22) percentage points and by 0.15 (95% C.I. 0.05; 0.26) percentage points compared to human insulin.
Clinical trials in patients with type 1 diabetes have demonstrated a reduced risk of nocturnal hypoglycaemia with insulin aspart compared with soluble human insulin. The risk of daytime hypoglycaemia was not significantly increased.
Children and Adolescents: A clinical trial comparing preprandial soluble human insulin with postprandial insulin aspart was performed in small children (26 patients 2-6 years) and a single dose PK/PD trial was performed in children (6-12 years) and adolescents (13-17 years). The pharmacodynamic profile of insulin aspart in children was similar to that seen in adults.
Pregnancy: The effect of pregnancy on the pharmacokinetics and pharmacodynamics of NovoRapid has not been studied (see Use in pregnancy & lactation under Precautions).
Insulin aspart is equipotent to soluble human insulin on a molar basis.
Pharmacokinetics: In NovoRapid substitution of the amino acid proline with aspartic acid at position B28 reduces the tendency to form hexamers as observed with soluble human insulin.
NovoRapid is therefore more rapidly absorbed from the SC layer compared to soluble human insulin. The time to maximum concentration is, on average, ½ of that for soluble human insulin. A mean maximum plasma concentration of 492±256 pmol/L was reached 40 (interquartile range: 30-40) mins after a SC dose of 0.15 U/kg bodyweight in type 1 diabetic patients. The insulin concentrations returned to baseline about 4-6 hrs after dose. The absorption rate was somewhat slower in type 2 diabetic patients, resulting in a lower Cmax (352±240 pmol/L) and later Tmax [60 (interquartile range: 50-90) mins]. The intra-individual variability in time to maximum concentration is significantly less for NovoRapid than for soluble human insulin, whereas the intra-individual variability in Cmax for NovoRapid is larger.
Elderly: The relative differences in pharmacokinetic properties between insulin aspart and soluble human insulin in elderly subjects (65-83 years, mean age 70 years) with type 2 diabetes were similar to those observed in healthy subjects and in younger subjects with diabetes. A decreased absorption rate was observed in elderly subjects, resulting in a later Tmax [82 (interquartile: 60-120) min], whereas Cmax was similar to that observed in younger subjects with type 2 diabetes and slightly lower than in subjects with type 1 diabetes.
Hepatic Impairment: A single dose pharmacokinetic study of insulin aspart was performed in 24 subjects with hepatic function ranging from normal to severely impaired. In subjects with hepatic impairment absorption rate was decreased and more variable resulting in delayed Tmax from about 50 min in subjects with normal hepatic function to about 85 min in subjects with moderate and severe hepatic impairment. AUC, Cmax and CL/F were similar in subjects with reduced hepatic function compared with subjects with normal hepatic function.
Renal Impairment: A single dose pharmacokinetic study of insulin aspart in 18 subjects with renal function ranging from normal to severely impaired was performed. No apparent effect of creatinine clearance values on AUC, Cmax, CL/F and Tmax of insulin aspart was found. Data were limited in subjects with moderate and severe renal impairment. Subjects with renal failure necessitating dialysis treatment were not investigated.
Children and Adolescents: The pharmacokinetic and pharmacodynamic properties of NovoRapid were investigated in children (6-12 years) and adolescents (13-17 years) with type 1 diabetes. Insulin aspart was rapidly absorbed in both age groups, with similar Tmax as in adults.
However, Cmax differed between the age groups, stressing the importance of the individual titration of NovoRapid.
Toxicology: Preclinical Safety Data: Non-clinical data reveal no special hazard for humans based on conventional studies of safety pharmacology, repeated dose toxicity, genotoxicity and toxicity to reproduction.
In in vitro tests, including binding to insulin and IGF-1 receptor sites and effects on cell growth, insulin aspart behaved in a manner that closely resembled human insulin. Studies also demonstrate that the dissociation of binding to the insulin receptor of insulin aspart is equivalent to human insulin.
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