The terminal half-life of NNC0113-0217 is estimated to be 8 h in the
mouse, 11 hr in the rat, 28 h in the rabbit and 51 h in the monkey.
NNC0113-0217 has been tested in a range of diabetic and obese animal
models. In normal male rats, the in vivo potency was
estimated by dosing NNC0113-0217 subcutaneously (s.c.) followed by an
i.v. glucose infusion 3 hrs later. NNC0113-0217 stimulated plasma
insulin secretion and lowered blood glucose at a dose of 123 ug/kg.
In male diabetic db/db mice, upon single or repeated 4 week
s.c. dosing, NNC0113-0217 lowers blood glucose dose-dependently and
has a long duration of action. The ED50 for lowering of blood glucose
(6 hours post dosing) is estimated to be 1.2 ug/kg for NNC0113-0217.
The maximal effect on blood glucose lowering was obtained at 4-8 ug/kg
for NNC0113-0217 in the 4 week study. The effect on body weight was
maximal at a dose of 21 ug/kg.
The effects of NNC0113-0217 on body weight regulation have been
evaluated in high fat diet obese (DIO) mice. Dosing of NNC0113-0217
for 18 days (0.15 mg/kg, s.c., daily) significantly lowered body weight.
When administering NNC0113-0217 to animals it is necessary to do dose
titrations. A good dose for pharmacological experiments could be 120
ug/kg once daily titrated up from 12 ug/kg to 40 ug/kg to 120 ug/kg.