Dataset Information

Comparative pharmacokinetics and insulin action for three rapid-acting insulin analogs injected subcutaneously with and without hyaluronidase.

ABSTRACT:

Objective

To compare the pharmacokinetics and glucodynamics of three rapid-acting insulin analogs (aspart, glulisine, and lispro) injected subcutaneously with or without recombinant human hyaluronidase (rHuPH20).

Research design and methods

This double-blind six-way crossover euglycemic glucose clamp study was conducted in 14 healthy volunteers. Each analog was injected subcutaneously (0.15 units/kg) with or without rHuPH20.

Results

The commercial formulations had comparable insulin time-exposure and time-action profiles as follows: 50% exposure at 123-131 min and 50% total glucose infused at 183-186 min. With rHuPH20, the analogs had faster yet still comparable profiles: 50% exposure at 71-79 min and 50% glucose infused at 127-140 min. The accelerated absorption with rHuPH20 led to twice the exposure in the first hour and half the exposure beyond 2 h, which resulted in 13- to 25-min faster onset and 40- to 49-min shorter mean duration of insulin action.

Conclusions

Coinjection of rHuPH20 with rapid-acting analogs accelerated insulin exposure, producing an ultra-rapid time-action profile with a faster onset and shorter duration of insulin action.

SUBMITTER: Morrow L

PROVIDER: S-EPMC3554283 | biostudies-literature | 2013 Feb

REPOSITORIES: biostudies-literature

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Publications

Comparative pharmacokinetics and insulin action for three rapid-acting insulin analogs injected subcutaneously with and without hyaluronidase.

Morrow Linda L Muchmore Douglas B DB Hompesch Marcus M Ludington Elizabeth A EA Vaughn Daniel E DE

Diabetes care 20121005 2

<h4>Objective</h4>To compare the pharmacokinetics and glucodynamics of three rapid-acting insulin analogs (aspart, glulisine, and lispro) injected subcutaneously with or without recombinant human hyaluronidase (rHuPH20).<h4>Research design and methods</h4>This double-blind six-way crossover euglycemic glucose clamp study was conducted in 14 healthy volunteers. Each analog was injected subcutaneously (0.15 units/kg) with or without rHuPH20.<h4>Results</h4>The commercial formulations had comparabl ...[more]

PMID: 23043164

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Project description:ImportancePrevious studies have found that the risk of severe hypoglycemia does not differ between long-acting insulin analogs and neutral protamine Hagedorn (NPH) insulin in patients with type 2 diabetes. However, these studies did not focus on patients 65 years or older, who are at an increased risk for hypoglycemia, or did not include patients with concomitant prandial insulin use.ObjectiveTo examine the risk of emergency department (ED) visits or hospitalizations for hypoglycemia among older community-residing patients with type 2 diabetes who initiated long-acting insulin or NPH insulin in real-world settings.Design, setting, and participantsThis retrospective, new-user cohort study assessed Medicare beneficiaries 65 years or older who initiated insulin glargine (n = 407 018), insulin detemir (n = 141 588), or NPH insulin (n = 26 402) from January 1, 2007, to July 31, 2019.ExposuresInsulin glargine, insulin detemir, and NPH insulin.Main outcomes and measuresThe primary outcome was time to first ED visit or hospitalization for hypoglycemia, defined using a modified validated algorithm. Propensity score-weighted Cox proportional hazards regression was used to estimate hazard ratios (HRs) and 95% CIs. The risk of recurring hypoglycemia events was estimated using the Andersen-Gill model. Post hoc analyses were conducted investigating possible effect modification by age.ResultsOf the 575 008 patients initiating use of insulin (mean [SD] age 74.9 [6.7] years; 53% female), 407 018 used glargine, 141 588 used detemir, and 26 402 used NPH insulin. The study included 7347 ED visits or hospitalizations for hypoglycemia (5194 for glargine, 1693 for detemir, and 460 for NPH insulin, with a median follow-up across the 3 cohorts of 0.37 years (interquartile range, 0.20-0.76 years). Initiation of glargine and detemir use was associated with a reduced risk of hypoglycemia compared with NPH insulin use (HR for glargine vs NPH insulin, 0.71; 95% CI, 0.63-0.80; HR, detemir vs NPH insulin, 0.72; 95% CI, 0.63-0.82). The HRs were similar for the recurrent event analysis. The protective association of long-acting insulin analogs varied by age and was not seen with concomitant prandial insulin use.Conclusions and relevanceIn this cohort study, initiation of long-acting analogs was associated with a lower risk of ED visits or hospitalizations for hypoglycemia compared with NPH insulin in older patients with type 2 diabetes in Medicare. However, this association was not seen with concomitant prandial insulin use.

Dataset Information

Comparative pharmacokinetics and insulin action for three rapid-acting insulin analogs injected subcutaneously with and without hyaluronidase.

Objective

Research design and methods

Results

Conclusions

Publications

Comparative pharmacokinetics and insulin action for three rapid-acting insulin analogs injected subcutaneously with and without hyaluronidase.

Similar Datasets

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