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

2017; Cell Press; Volume: 26; Issue: 2 Linguagem: Inglês

10.1016/j.cmet.2017.07.011

1932-7420

Juan P. Frías, Edward J. Bastyr, Louis Vignati, Matthias H. Tschöp, Christophe Schmitt, K Owen, Rune Haubo Bojesen Christensen, Richard D. DiMarchi,

Metabolism, Diabetes, and Cancer

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.