The Sustained Effects of a Dual GIP/GLP-1 Receptor Agonist, NNC0090-2746, in Patients with Type 2 Diabetes

Publication date: 1 August 2017
Source:Cell Metabolism, Volume 26, Issue 2
Author(s): Juan Pablo Frias, Edward J. Bastyr, Louis Vignati, Matthias H. Tschöp, Christophe Schmitt, Klara Owen, Rune Haubo Christensen, Richard D. DiMarchi
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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Teaser

Frias et al. assessed the effects of NNC0090-2746, a unimolecular dual agonist derived from hybridized GLP-1 and GIP, in patients with T2DM. NNC0090-2746 was well tolerated and significantly improved glycemic control and reduced body weight compared with placebo. Maximum benefit was obtained by patients with the best baseline glycemic control.


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