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Frias, J.P.* ; Bastyr, E.J.* ; Vignati, L.* ; Tschöp, M.H. ; Schmitt, C.* ; Owen, K.R.* ; Christensen, R.H.* ; DiMarchi, R.D.*

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

Cell Metab. 26, 343-352.e2 (2017)

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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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Publication type Article: Journal article

Document type Scientific Article

Corresponding Author

Keywords Gip ; Glp-1 ; Dual Gip/glp-1 Agonist ; Metabolic Disease ; Pharmacodynamics ; Safety ; Type 2 Diabetes

ISSN (print) / ISBN 1550-4131

e-ISSN 1932-7420

Journal Cell Metabolism

Quellenangaben Volume: 26, Issue: 2, Pages: 343-352.e2

Publisher Elsevier

Non-patent literature Publications

Reviewing status Peer reviewed

Institute(s) Institute of Diabetes and Obesity (IDO)