Comparison of pharmacodynamics and pharmacokinetics of insulin degludec and insulin glargine 300 U/mL in healthy cats

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 (T-PEAK) of IGla-U300 was 145 +/- 114 min (95% confidence interval [CI] = 25-264) longer than T-PEAK of IDeg (P = 0.03) and duration of action (TOUR) of IGla-U300 was 250 +/- 173 min (95% CI = 68-432) longer than T-DUR of IDeg (P = 0.02). The "flatness" of the time-action profile (as represented by the quotient of peak action/T-DUR) 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. (C) 2019 Elsevier Inc. All rights reserved.