Results from three phase 1 trials of NNC9204-1177, a glucagon/GLP-1 receptor co-agonist: Effects on weight loss and safety in adults with overweight or obesity

• DOI: 10.1016/j.molmet.2023.101801
• Publication Date: 2023-09-09T08:58:28Z
• Authors: Martin Haljeta Fr...; Lars Endahl; Frederik Flindt K...; Ronald Goldwater; Martin Kankam; Søren Toubro; Sune Boris Nygård
• Keywords: Tolerability; Pharmacodynamics

Glucagon/glucagon-like peptide-1 (GLP-1) receptor co-agonists may provide greater weight loss than agonists targeting the GLP-1 alone. We report results from three phase 1 trials investigating safety, tolerability, pharmacokinetics and pharmacodynamics of glucagon/GLP-1 co-agonist NNC9204-1177 (NN1177) for once-weekly subcutaneous use in adults with overweight or obesity. Our focus was a 12-week, multiple ascending dose (MAD), placebo-controlled, double-blind trial which (N=99) received NN1177 (on an escalating regimen 200, 600, 1,300, 1,900, 2,800, 4,200 6,000 μg) placebo. Two other also contributed to findings reported this article: first human (FHD)/single (SAD), (N=49) (treatment doses 10, 40, 120, 350, 700 1,100 placebo, drug–drug interaction, open-label, single-sequence (N=45) 4,200-μg NN1177, following administration Cooperstown 5+1 index cocktail. Safety, pharmacokinetic pharmacodynamic endpoints were assessed. For FHD/SAD MAD trials, baseline characteristics generally balanced across treatment cohorts. The geometric mean half-life at steady state estimated between 77 111 hours, clinically relevant achieved (up 12.6% week 12; μg trial). Although appeared tolerable several unexpected treatment-related safety signals observed; increased heart rate, decreased reticulocyte count, markers inflammation (fibrinogen C-reactive protein), aspartate alanine aminotransferase, impaired glucose tolerance reduced blood levels some amino acids. associated dose-dependent loss, observed precluded further clinical development.