Pharmacodynamics and pharmacokinetics of insulin detemir and insulin glargine 300 U/mL in healthy dogs

H. Fink, C. Herbert, Chen Gilor

Research output: Contribution to journalArticle

Abstract

Insulin glargine 300 U/mL and insulin detemir are synthetic long-acting insulin analogs associated with minimal day-to-day variability or episodes of hypoglycemia in people. Here, 8 healthy purpose-bred dogs each received 2.4 nmol/kg subcutaneous injections of insulin detemir (0.1 U/kg) and insulin glargine 300 U/mL (0.4 U/kg) on 2 different days, >1 wk apart, in random order. Blood glucose (BG) was measured every 5 min, and glucose was administered intravenously at a variable rate with the goal of maintaining BG within 10% of baseline BG (“isoglycemic clamp”). Endogenous and exogenous insulin were measured for up to 24 h after insulin injection. The effect of exogenous insulin was defined by glucose infusion rate or a decline in endogenous insulin. Isoglycemic clamps were generated in all 8 dogs after detemir but only in 4 dogs after glargine. Median time to onset of action was delayed with glargine compared to detemir (4.0 h [3.3–5.8 h] vs 0.6 h [0.6–1.2 h], P = 0.002). There was no difference in time to peak (median [range] = 6.3 h [5.0–21.3 h] vs 4.3 h [2.9–7.4 h], P = 0.15) or duration of action (16.3 h [6.1–20.1 h] vs 10.8 h [8.8–14.8 h], P = 0.21) between glargine and detemir, respectively. Glargine demonstrated a peakless time-action profile in 4/8 dogs. The total metabolic effect and peak action of detemir was significantly greater than glargine. Significant concentrations of glargine were detected in all but 1 dog following administration. Glargine might be better suited than detemir as a once-daily insulin formulation in some dogs based on its long duration of action and peakless time-action profile. Day-to-day variability in insulin action should be further assessed for both formulations.

Original languageEnglish (US)
Pages (from-to)17-30
Number of pages14
JournalDomestic Animal Endocrinology
Volume64
DOIs
StatePublished - Jul 1 2018

Fingerprint

pharmacology
pharmacokinetics
insulin
Pharmacokinetics
Dogs
dogs
Insulin
Blood Glucose
blood glucose
Long-Acting Insulin
Insulin Detemir
Insulin Glargine
Glucose
Glucose Clamp Technique
Subcutaneous Injections
glucose
Hypoglycemia
duration
hypoglycemia
subcutaneous injection

Keywords

  • Diabetes mellitus
  • Isoglycemic clamp

ASJC Scopus subject areas

  • Food Animals
  • Animal Science and Zoology
  • Endocrinology

Cite this

Pharmacodynamics and pharmacokinetics of insulin detemir and insulin glargine 300 U/mL in healthy dogs. / Fink, H.; Herbert, C.; Gilor, Chen.

In: Domestic Animal Endocrinology, Vol. 64, 01.07.2018, p. 17-30.

Research output: Contribution to journalArticle

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abstract = "Insulin glargine 300 U/mL and insulin detemir are synthetic long-acting insulin analogs associated with minimal day-to-day variability or episodes of hypoglycemia in people. Here, 8 healthy purpose-bred dogs each received 2.4 nmol/kg subcutaneous injections of insulin detemir (0.1 U/kg) and insulin glargine 300 U/mL (0.4 U/kg) on 2 different days, >1 wk apart, in random order. Blood glucose (BG) was measured every 5 min, and glucose was administered intravenously at a variable rate with the goal of maintaining BG within 10{\%} of baseline BG (“isoglycemic clamp”). Endogenous and exogenous insulin were measured for up to 24 h after insulin injection. The effect of exogenous insulin was defined by glucose infusion rate or a decline in endogenous insulin. Isoglycemic clamps were generated in all 8 dogs after detemir but only in 4 dogs after glargine. Median time to onset of action was delayed with glargine compared to detemir (4.0 h [3.3–5.8 h] vs 0.6 h [0.6–1.2 h], P = 0.002). There was no difference in time to peak (median [range] = 6.3 h [5.0–21.3 h] vs 4.3 h [2.9–7.4 h], P = 0.15) or duration of action (16.3 h [6.1–20.1 h] vs 10.8 h [8.8–14.8 h], P = 0.21) between glargine and detemir, respectively. Glargine demonstrated a peakless time-action profile in 4/8 dogs. The total metabolic effect and peak action of detemir was significantly greater than glargine. Significant concentrations of glargine were detected in all but 1 dog following administration. Glargine might be better suited than detemir as a once-daily insulin formulation in some dogs based on its long duration of action and peakless time-action profile. Day-to-day variability in insulin action should be further assessed for both formulations.",
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