KBP-066A, a long-acting dual amylin and calcitonin receptor agonist, induces weight loss and improves glycemic control in obese and diabetic rats.

ABSTRACT:

Objective

Dual amylin and calcitonin receptor agonists (DACRAs) are novel therapeutic agents that not only improve insulin sensitivity but also work as an adjunct to established T2DM therapies. DACRAs are currently administered once daily, though it is unknown whether DACRAs with increased plasma half-life can be developed as a once-weekly therapy.

Methods

The in vitro potencies of the KBP-066A and KBP-066 (non-acylated) were assessed using reporter assays. Acylation functionality was investigated by a combination of pharmacokinetics and acute food intake in rats. in vivo efficacies were investigated head-to-head in obese (HFD) and T2D (ZDF) models.

Results

In in vitro, KBP-066A activated the CTR and AMY-R potently, with no off-target activity. Acylation functionality

SUBMITTER: Andreassen KV 

PROVIDER: S-EPMC8313742 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature