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Finan, B.* ; Douros, J.D.* ; Goldwater, R.* ; Hansen, A.M.K.* ; Hjerpsted, J.B.* ; Hjøllund, K.R.* ; Kankam, M.K.* ; Knerr, P.J.* ; Konkar, A.* ; Mowery, S.A.* ; Müller, T.D. ; Nielsen, J.R.* ; Nygård, S.B.* ; Perez-Tilve, D.* ; Raun, K.* ; Yang, B.* ; Tschöp, M.H. ; DiMarchi, R.D.*

A once-daily GLP-1/GIP/glucagon receptor tri-agonist (NN1706) lowers body weight in rodents, monkeys and humans.

Mol. Metab. 96:102129 (2025)
DOI PMC
Open Access Gold as soon as Publ. Version/Full Text is submitted to ZB.
Single molecules that combine complementary modes of action with glucagon-like peptide-1 receptor (GLP-1R) agonism are best-in-class therapeutics for obesity treatment. NN1706 (MAR423, RO6883746) is a fatty-acylated tri-agonist designed for balanced activity at GLP-1R and glucose-dependent insulinotropic polypeptide receptor (GIPR) with lower relative potency at the glucagon receptor (GcgR). Obese mice, rats and non-human primates dosed with NN1706 showed significant body weight reductions and improved glycemic control. In human participants with overweight or obesity, daily subcutaneous NN1706 treatment resulted in substantial body weight loss in a dose-dependent manner without impairing glycemic control (NCT03095807, NCT03661879). However, increased heart rate was observed across NN1706 treatment cohorts, which challenges further clinical development of NN1706.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Clinical ; Glucagon ; Incretins ; Obesity
ISSN (print) / ISBN 2212-8778
e-ISSN 2212-8778
Journal Molecular Metabolism
Quellenangaben Volume: 96, Issue: , Pages: , Article Number: 102129 Supplement: ,
Publisher Elsevier
Publishing Place Amsterdam
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Diabetes and Obesity (IDO)