Time-action profiles of insulin detemir in normal and diabetic dogs

Update on insulin treatment of dogs and cats with non-complicated diabetes mellitus

“…In cats, due to its short duration of action, insulin NPH results in poor glycemic control when administered BID (Zerrenner et al, 2007). Insulin NPH is commonly used for the treatment of canine DM, especially overseas (Aptekmann and Schwartz, 2011), and less frequently for feline DM, at an initial dose of 0.25-0.5 U kg -1 BID that can be subsequently increased by 10-15% or decreased by 25% in case of persistent hyperglycemia (>250 mg dl ), respectively (Cook, 2007;Zerrenner et al, 2007;Sako et al, 2011).…”

“…On the contrary, in diabetic cats insulin glargine treatment is clearly superior and carries an increased potential for diabetic remission (see later) compared to insulin lente and PZI (Marshall et al, 2009;) which explains why, despite its recent introduction into the market and lack of a veterinary formulation, it is the preferred insulin for treatment of feline DM for more than 25% of the veterinarians in the U.S.A. (Smith et al, 2012). However, a recent analysis did not demonstrate a benefit of insulin glargine over insulin lente of porcine origin in terms of the duration of survival of diabetic cats (Callegari et al, 2013) Insulin detemir (Levemir ® , 100 U ml -1 , Novo Nordisk) is also a recombinant human insulin analogue where threonine has been removed from the C-terminal of B chain and myristic acid has been bound to the lysine which is 29 th amino acid of the same chain (Gilor et al, 2010;Sako et al, 2011;. These molecular changes result in a slowly absorbed and highly albumin-bound molecule with long duration of action and increased the duration of action was found to be 24h in normal dogs and the blood glucose lowering-effect is similar or slightly lower compared to insulin NPH (Mori et al, 2008;Sako et al, 2011).…”

“…However, a recent analysis did not demonstrate a benefit of insulin glargine over insulin lente of porcine origin in terms of the duration of survival of diabetic cats (Callegari et al, 2013) Insulin detemir (Levemir ® , 100 U ml -1 , Novo Nordisk) is also a recombinant human insulin analogue where threonine has been removed from the C-terminal of B chain and myristic acid has been bound to the lysine which is 29 th amino acid of the same chain (Gilor et al, 2010;Sako et al, 2011;. These molecular changes result in a slowly absorbed and highly albumin-bound molecule with long duration of action and increased the duration of action was found to be 24h in normal dogs and the blood glucose lowering-effect is similar or slightly lower compared to insulin NPH (Mori et al, 2008;Sako et al, 2011). In cats pharmacokinetics and pharmacodynamics vary between patients so that a clear nadir of blood glucose concentration may or may not be seen; onset of action occurs after approximately 1-2h, glucose nadir may be seen any time between 2.5 and 16h, sometimes a biphasic action with an early and a late nadir is noticed and the duration of action varies between 7h and 24h but in most cats it exceeds 12h Rios and Ward, 2008;Gilor et al, 2010;Smith et al, 2012).…”

“…For cats with DM insulin glargine treatment is started at 0.25-0.5 U kg -1 BID (the upper end of the dosing regimen is used when blood glucose concentration exceeds 360 mg dl -1 ) or at 1-2 U per cat BID depending on the ideal body weight (1 U if ≤4 kg and 1.5-2 U if >4 kg) (Cook, 2007;Rios and Ward, 2008;Hall et al, 2009;Marshall et al, 2009;Tschuor et al, 2011). Some investigators advocate to adjust the initial dose by hospitalizing cats and performing serial J HELLENIC , 67(2) ΠΕΚΕ 2016 liver penetration (Gilor et al, 2010;Sako et al, 2011; which is also very stable and can be used for up to 6 weeks after opening if kept at room temperature and up to 6 months if refrigerated . In normal dogs peak activity is witnessed at 8-10h and the duration of action is more than 24h (Sako et al, 2011), whereas the respective figures in cats are 5-9h (average: 7h) and 9-14h (average: 12h) (Gilor et al, 2010).…”

“…Some investigators advocate to adjust the initial dose by hospitalizing cats and performing serial J HELLENIC , 67(2) ΠΕΚΕ 2016 liver penetration (Gilor et al, 2010;Sako et al, 2011; which is also very stable and can be used for up to 6 weeks after opening if kept at room temperature and up to 6 months if refrigerated . In normal dogs peak activity is witnessed at 8-10h and the duration of action is more than 24h (Sako et al, 2011), whereas the respective figures in cats are 5-9h (average: 7h) and 9-14h (average: 12h) (Gilor et al, 2010). In general the pharmacokinetics vary among cats, the time-action profile can either be long-acting without peaks or shorter-acting with a demonstrable nadir of blood glucose concentration and the duration of action is shorter compared to humans (Gilor et al, 2010).…”