Abstract
Insulin glargine 300 U/mL (IGla-U300) and insulin degludec (IDeg) are synthetic insulin analogs designed as basal insulin formulations. In people, IGla-U300 is more predictable and longer acting compared with glargine 100 U/mL. The duration of action of IDeg in people is > 42 h, allowing flexibility in daily administration. We hypothesized that IDeg would have longer duration of action compared with IGla-U300 in healthy purpose-bred cats. Seven cats received 0.4 U/kg (subcutaneous) of IDeg and IGla-U300 on two different days, >1 wk apart. Exogenous insulin was measured and pharmacodynamic parameters were derived from glucose infusion rates during isoglycemic clamps and suppression of endogenous insulin. The Shapiro-Wilk test was used to assess normality, and normally distributed parameters were compared using paired t-tests. There was no difference between IDeg and IGla-U300 in onset, peak action, or total metabolic effect. On average, time to peak action (TPEAK) of IGla-U300 was 145 ± 114 min (95% confidence interval [CI] = 25–264) longer than TPEAK of IDeg (P = 0.03) and duration of action (TDUR) of IGla-U300 was 250 ± 173 min (95% CI = 68–432) longer than TDUR of IDeg (P = 0.02). The “flatness” of the time-action profile (as represented by the quotient of peak action/TDUR) was significantly greater for IGla-U300 compared with IDeg (P = 0.04). Overall, insulin concentration measurements concurred with findings from isoglycemic clamps. Based on these data, IDeg is not suitable for once-daily administration in cats. The efficacy of once-daily IGla-U300 in diabetic cats should be further investigated.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 19-29 |
| Number of pages | 11 |
| Journal | Domestic Animal Endocrinology |
| Volume | 69 |
| DOIs | |
| State | Published - Oct 1 2019 |
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Keywords
- Diabetes mellitus
- Isoglycemic clamp
ASJC Scopus subject areas
- Food Animals
- Animal Science and Zoology
- Endocrinology
Cite this
Comparison of pharmacodynamics and pharmacokinetics of insulin degludec and insulin glargine 300 U/mL in healthy cats. / Gilor, C.; Culp, W.; Ghandi, S.; do Carmo Emidio e Silva, J. A.; Ladhar, A.; Hulsebosch, S.
In: Domestic Animal Endocrinology, Vol. 69, 01.10.2019, p. 19-29.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Comparison of pharmacodynamics and pharmacokinetics of insulin degludec and insulin glargine 300 U/mL in healthy cats
AU - Gilor, C.
AU - Culp, W.
AU - Ghandi, S.
AU - do Carmo Emidio e Silva, J. A.
AU - Ladhar, A.
AU - Hulsebosch, S.
PY - 2019/10/1
Y1 - 2019/10/1
N2 - Insulin glargine 300 U/mL (IGla-U300) and insulin degludec (IDeg) are synthetic insulin analogs designed as basal insulin formulations. In people, IGla-U300 is more predictable and longer acting compared with glargine 100 U/mL. The duration of action of IDeg in people is > 42 h, allowing flexibility in daily administration. We hypothesized that IDeg would have longer duration of action compared with IGla-U300 in healthy purpose-bred cats. Seven cats received 0.4 U/kg (subcutaneous) of IDeg and IGla-U300 on two different days, >1 wk apart. Exogenous insulin was measured and pharmacodynamic parameters were derived from glucose infusion rates during isoglycemic clamps and suppression of endogenous insulin. The Shapiro-Wilk test was used to assess normality, and normally distributed parameters were compared using paired t-tests. There was no difference between IDeg and IGla-U300 in onset, peak action, or total metabolic effect. On average, time to peak action (TPEAK) of IGla-U300 was 145 ± 114 min (95% confidence interval [CI] = 25–264) longer than TPEAK of IDeg (P = 0.03) and duration of action (TDUR) of IGla-U300 was 250 ± 173 min (95% CI = 68–432) longer than TDUR of IDeg (P = 0.02). The “flatness” of the time-action profile (as represented by the quotient of peak action/TDUR) was significantly greater for IGla-U300 compared with IDeg (P = 0.04). Overall, insulin concentration measurements concurred with findings from isoglycemic clamps. Based on these data, IDeg is not suitable for once-daily administration in cats. The efficacy of once-daily IGla-U300 in diabetic cats should be further investigated.
AB - Insulin glargine 300 U/mL (IGla-U300) and insulin degludec (IDeg) are synthetic insulin analogs designed as basal insulin formulations. In people, IGla-U300 is more predictable and longer acting compared with glargine 100 U/mL. The duration of action of IDeg in people is > 42 h, allowing flexibility in daily administration. We hypothesized that IDeg would have longer duration of action compared with IGla-U300 in healthy purpose-bred cats. Seven cats received 0.4 U/kg (subcutaneous) of IDeg and IGla-U300 on two different days, >1 wk apart. Exogenous insulin was measured and pharmacodynamic parameters were derived from glucose infusion rates during isoglycemic clamps and suppression of endogenous insulin. The Shapiro-Wilk test was used to assess normality, and normally distributed parameters were compared using paired t-tests. There was no difference between IDeg and IGla-U300 in onset, peak action, or total metabolic effect. On average, time to peak action (TPEAK) of IGla-U300 was 145 ± 114 min (95% confidence interval [CI] = 25–264) longer than TPEAK of IDeg (P = 0.03) and duration of action (TDUR) of IGla-U300 was 250 ± 173 min (95% CI = 68–432) longer than TDUR of IDeg (P = 0.02). The “flatness” of the time-action profile (as represented by the quotient of peak action/TDUR) was significantly greater for IGla-U300 compared with IDeg (P = 0.04). Overall, insulin concentration measurements concurred with findings from isoglycemic clamps. Based on these data, IDeg is not suitable for once-daily administration in cats. The efficacy of once-daily IGla-U300 in diabetic cats should be further investigated.
KW - Diabetes mellitus
KW - Isoglycemic clamp
UR - http://www.scopus.com/inward/record.url?scp=85068269000&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85068269000&partnerID=8YFLogxK
U2 - 10.1016/j.domaniend.2019.04.001
DO - 10.1016/j.domaniend.2019.04.001
M3 - Article
C2 - 31280022
AN - SCOPUS:85068269000
VL - 69
SP - 19
EP - 29
JO - Domestic Animal Endocrinology
JF - Domestic Animal Endocrinology
SN - 0739-7240
ER -