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 language | English (US) |
|---|---|
| Pages (from-to) | 17-30 |
| Number of pages | 14 |
| Journal | Domestic Animal Endocrinology |
| Volume | 64 |
| DOIs | |
| State | Published - Jul 1 2018 |
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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 journal › Article
}
TY - JOUR
T1 - Pharmacodynamics and pharmacokinetics of insulin detemir and insulin glargine 300 U/mL in healthy dogs
AU - Fink, H.
AU - Herbert, C.
AU - Gilor, Chen
PY - 2018/7/1
Y1 - 2018/7/1
N2 - 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.
AB - 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.
KW - Diabetes mellitus
KW - Isoglycemic clamp
UR - http://www.scopus.com/inward/record.url?scp=85046429971&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85046429971&partnerID=8YFLogxK
U2 - 10.1016/j.domaniend.2018.03.007
DO - 10.1016/j.domaniend.2018.03.007
M3 - Article
C2 - 29709796
AN - SCOPUS:85046429971
VL - 64
SP - 17
EP - 30
JO - Domestic Animal Endocrinology
JF - Domestic Animal Endocrinology
SN - 0739-7240
ER -