Differences in Pharmacokinetics and Pharmacodynamics of Insulin Lispro and Aspart in Healthy Volunteers

Abstract

Pharmacokinetic and pharmacodynamic profiles of the rapid-acting insulin analogues lispro and aspart were compared in a randomized, double-blind crossover study of 20 fasting healthy men following a single subcutaneous injection. Either insulin lispro or aspart, 0.05 U/kg-body-weight, was injected subcutaneously and followed by determination of 5-h profiles of plasma glucose, serum C-peptide and insulin concentrations. Lowest glucose concentrations were observed after 50 min in the aspart group (3.2 +/- 0.1 mmol/l versus lispro 3.5 +/- 0.1 mmol/l; p = 0.026) and after 60 min in the lispro group (3.4 +/- 0.1 mmol/l). For blood glucose t min was 59.3 +/- 3.4 min in the aspart and 63.5 +/- 5.3 min in the lispro group (ns). After 40 min a lower C-peptide was determined for aspart (225 +/- 21 pmol/l versus lispro 309 +/- 33 pmol/l; p = 0.031), whereas minimal C-peptide concentrations were reached in both groups after 105 min (lispro 117 +/- 21 pmol/l versus aspart 105 +/- 18 pmol/l). The maximal concentration of insulin was detected in both groups after 40 min (lispro 20.8 +/- 1.1 mU/l versus aspart 24.6 +/- 1.3 mU/l; p = 0.032). For insulin t max was 33.0 +/- 2.6 min in the aspart versus 33.3 +/- 2.6 min in the lispro group (ns). The present results indicate a more rapid absorption of insulin aspart in comparison to insulin lispro. Higher insulin concentrations after subcutaneus injection may be advantageous in meal-related treatment of diabetes.

Experiences of a Poison Center Network with Renal Insufficiency in Acetaminophen Overdose: An Analysis of 17 Cases

“…Unfortunately, acetaminophen was confirmed by blood testing in only 7 of the 17 patients and many patients presented after a period of time after ingestion when no considerable amount of acetaminophen (half life 1-4 hours) could be expected to be in the blood due to pharmacokinetic reasons (23,24). The authors were aware of the fact that the recruitment of the subjects under consideration was based solely on the information of physicians contacting the poison center network.…”

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

“…In studies that have directly compared the absorption rate and glucose control of one rapid‐acting insulin analogue with another, few PK/PD differences have been noted. Of five studies that compared insulin lispro and insulin aspart, only two detected a significant difference [13–17]. In one of them, a randomized, crossover trial in 14 people with type 1 diabetes, subcutaneous injection of insulin lispro reached maximum insulin concentration significantly earlier than insulin aspart (p = 0.02) and declined to 50% of the peak insulin concentration significantly earlier (p = 0.02) [13].…”

“…References from retrieved publications provided additional material and were used to expand the period of time from which data were assembled. A total of 19 papers were identified with results of PK/PD studies for rapid-acting analogues: 11 for insulin lispro [10][11][12][13][14][15][16][17][18][19][20], 10 for insulin aspart [13][14][15][16][17][21][22][23][24][25] and 9 for insulin glulisine [11,[18][19][20]23,24,[26][27][28]. Some studies included more than one analogue.…”

Cumulative clinical experience with use of insulin lispro: critical appraisal, role in therapy, and patient considerations

“…An randomized double-blind study in healthy males comparing insulin lispro and aspart6 showed a 10-minute difference in the time to maximal reduction, favoring insulin aspart, but no difference in the glucose control response. Two studies done in patients with type 1 diabetes mellitus5,7 showed very similar peak times for both insulin aspart and lispro (approximately 40 minutes in both studies) and time to reach 50% of the peak (approximately 20 minutes).…”