The terminal half-life of NNC0090-1170 is around 14 h in pigs while
shorter in mice, rats, rabbits and monkeys (4-8 h).
NNC0090-1170 has been evaluated in several diabetic and obese animal
models. NNC0090-1170 shows a dose-dependent and long-lasting
anti-hyperglycaemic effect in ob/ob and db/db mice.
The mean area under the curve (AUC) for blood glucose is
dose-dependently reduced after a single subcutaneous injection of
NNC0090-1170 (30, 100, 300 or 1000 ug/kg). In db/db mice, the
ED50 for lowering of blood glucose (6 hours post dosing) is estimated
to be approximately 24 ug/kg following an acute dose. With twice daily
administration of 100 ug/kg NNC0090-1170 for two weeks, blood glucose
AUCs were significantly reduced in ob/ob mice. These
anti-hyperglyeamic effects are also observed in db/db mice
treated for 15 days with NNC0090-1170 (200 ug/kg twice daily s.c.).
In young ZDF rats, 6 week treatment with NNC0090-1170 (30 and 150
ug/kg twice daily s.c.) reduces blood glucose levels and insulin
levels following a glucose tolerance test. In candy-fed rats,
NNC0090-1170 (0.2 mg/kg, twice daily, s.c.) reduces food intake and
subsequently weight gain, especially fat mass.
When administering NNC0090-1170 to animals it is necessary to do dose
titrations. A good dose for pharmacological experiments could be 1
mg/kg once daily titrated up from 0.1 mg/kg to 0.3 mg/kg to 1.0 mg/kg.