Time-action profiles of insulin degludec in healthy dogs and its effects on glycemic control in diabetic dogs

Abstract

Insulin degludec (IDeg) is a new insulin formulation that facilitates long-term control of glucose level in humans. In this study, we investigated the effects of IDeg on glycemic control in dogs. Its time-action profiles were monitored in healthy dogs using an artificial pancreas apparatus under euglycemic conditions. At 9.0–13.5 hr post-IDeg injection, an indistinct peak of glucose level was detected. Moreover, the action of IDeg was persistent for >20 hr. Both IDeg and neutral protamine Hagedorn insulin (NPH) lowered blood glucose concentrations in diabetic dogs, but IDeg caused postprandial hyperglycemia and a somewhat lower preprandial glucose level than that caused by NPH. IDeg might be ineffective in concurrently preventing postprandial hyperglycemia and preprandial hypoglycemia in a single-agent administration.

Flash glucose monitoring in diabetic dogs: a feasible method for evaluating glycemic control

“…Further, low pre-and high postprandial glucose concentrations were common in the 5 dogs treated with the ultra-long acting basal insulin degludec. The high glycemic variability observed in these 2 groups of dogs can easily be explained by the specific time-action profiles of these insulins and has been described in earlier studies [38] [39]. Nevertheless, the fact that a low MAGE in combination with a low mean glucose concentration was observed in 2 dogs treated with porcine lente insulin and one dog treated with insulin degludec indicates that satisfying glycemic control is possible with the use of these insulins.…”

Day‐to‐day variability of porcine lente, insulin glargine 300 U/mL and insulin degludec in diabetic dogs

“…These results might reflect the fact that in terms of minimizing intraday oscillations, there is an advantage to increasing the frequency of feedings and insulin administration when using an insulin that peaks within a few hours after administration (like PL 17 ), coinciding with post prandial absorption of carbohydrates. In contrast, there is no advantage to increasing the frequency when using a true basal insulin that roughly exerts the same action evenly throughout a 24 hours period after a single injection (eg, IDeg 12 ). In fact, because a basal insulin does not curb post‐prandial hyperglycemia, splitting the daily food intake into 2 equal meals while using a basal insulin is expected to result in 2 major hyperglycemic excursions as seen in our data.…”

“…Insulin degludec (IDeg) is a recombinant‐human insulin analog formed by replacing the amino‐acid at the B30 position with hexadecandioic acid. It forms stable di‐hexamers in solution with phenol and zinc but generates soluble multihexamers after subcutaneous injection 12 . The dissociation of these multihexamers into monomers is slow and consistent, which helps reduce intra‐ and interday variability 13 .…”

“…In people, IDeg reaches steady‐state concentrations after a few days of once‐daily injections and can then be administered safely on a “flexible schedule,” without compromising glycemic control 3 . In dogs, IDeg was demonstrated to have a peakless time action profile with a duration of action greater than 20 hours 12 …”

The effect of Insulin Degludec on glycemic control in diabetic cats over a 12-month period

“…Previously, a clear difference among four different insulin preparations for dogs was demonstrated by examining their time-action profiles [9,14,18]. The action of IDeg was persistent for >20 hr, representing its long profile [14] as well as insulin detemir (IDet), and insulin glargine (IGla) [9,14,18]. However, the effects of IDeg have not yet been investigated in cats; therefore, in the current study, the effects of IDeg upon long-term glycemic control in diabetic cats were studied.…”