PT  - JOURNAL ARTICLE
AU  - Sara Toftegaard Hjuler
AU  - Sofie Gydesen
AU  - Kim Vietz Andreassen
AU  - Morten Asser Karsdal
AU  - Kim Henriksen
TI  - The Dual Amylin- and Calcitonin Receptor Agonist KBP-042 works as Adjunct to Metformin on Fasting Hyperglycaemia and HbA1c in a rat model of Type 2 Diabetes
AID  - 10.1124/jpet.117.241281
DP  - 2017 Jan 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - jpet.117.241281
4099  - http://jpet.aspetjournals.org/content/early/2017/04/24/jpet.117.241281.short
4100  - http://jpet.aspetjournals.org/content/early/2017/04/24/jpet.117.241281.full
AB  - KBP-042 is a dual amylin and calcitonin receptor agonist which increases glucose tolerance and insulin action, and reduces body weight in rat models of obesity and pre-diabetes. The objective of the present study was to 1) Evaluate KBP-042 as a treatment of late stage type 2 diabetes in a rat model and 2) Assess the value of adding KBP-042 to the standard of care, metformin, in order to consider KBP-042 as a relevant drug for treating patients with type 2 diabetes. Two studies were included: an intervention and a prevention study. Intervention: Treatment with 5 µg/kg KBP-042 was initiated in 11-weeks old ZDF rats. Glucose tolerance, fasting glycaemia as well as glycated haemoglobin were assessed after 4 weeks. Prevention: Either metformin (400 mg/kg), KBP-042 (5 µg/kg) or a combination of both were administered to ZDF rats for a total of 9 weeks. Glycaemia, glucose tolerance, and insulin tolerance were tested. Furthermore, fasting plasma insulin and glucagon levels were evaluated. Finally, pancreatic content of insulin was assessed as a surrogate marker of beta-cell mass. It was found that KBP-042 was efficient in lowering fasting plasma glucose as well as improving glucose tolerance, both as prevention and intervention of disease progression. Furthermore, KBP-042 was efficient in combination with metformin and had additional effects compared to either therapy alone. In conclusion, KBP-042 is a highly relevant therapeutic candidate against type 2 diabetes, effective both as add-on to metformin and as stand-alone therapy.