[PDF][PDF] The sustained effects of a dual GIP/GLP-1 receptor agonist, NNC0090-2746, in patients with type 2 diabetes

JP Frias, EJ Bastyr, L Vignati, MH Tschoep, C Schmitt… - Cell Metabolism, 2017 - cell.com
Cell Metabolism, 2017cell.com
Unimolecular dual incretins derived from hybridized glucagon-like peptide 1 (GLP-1) and
glucose-dependent insulinotropic peptide (GIP) sequences have demonstrated synergistic
reduction of adiposity in animal models and reductions of hyperglycemia in short-duration
human trials. Here, we extend the characterization of NNC0090-2746 (also known as
RG7697), a fatty-acylated dual agonist possessing in vitro balanced GIPR and GLP-1R
agonism. In this 12-week, randomized, placebo-controlled, double-blind phase 2a trial …
Summary
Unimolecular dual incretins derived from hybridized glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) sequences have demonstrated synergistic reduction of adiposity in animal models and reductions of hyperglycemia in short-duration human trials. Here, we extend the characterization of NNC0090-2746 (also known as RG7697), a fatty-acylated dual agonist possessing in vitro balanced GIPR and GLP-1R agonism. In this 12-week, randomized, placebo-controlled, double-blind phase 2a trial, patients with type 2 diabetes inadequately controlled with metformin received 1.8 mg of NNC0090-2746 or placebo subcutaneously once daily. Liraglutide 1.8 mg (Victoza), starting with 2-week dose escalation, was administered subcutaneously once daily as an open-label reference arm. Measurements were collected at regular intervals after randomization. NNC0090-2746 significantly improved glycemic control and reduced body weight compared with placebo. Total cholesterol, alone among a range of lipid parameters, and leptin were both significantly reduced compared with placebo. Treatment with NNC0090-2746 was generally safe and well tolerated.
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