NN1177 / Novo Nordisk - LARVOL DELTA

In vitro CYP450 enzyme down-regulation by GLP-1/glucagon co-agonist does not translate to observed drug-drug interactions in the clinic. (PubMed, Drug Metab Dispos) - "The study enrolled 45 study participants (BMI 23.0-29.9 kg/m) to receive a Cooperstown 5+1 cocktail (midazolam, caffeine, omeprazole, dextromethorphan, and S-warfarin/vitamin K) alone and following steady state NN1177 exposure. Significance Statement This study highlights significant challenges associated with assessing drug-drug interaction risks for therapeutic peptides using in vitro systems, since potential concerns identified by standard assays did not translate to the clinical setting. Further research is required to guide investigators involved in peptide-based drug development towards better non-clinical models in order to more accurately evaluate potential drug-drug interactions."

Journal • Preclinical • Addiction (Opioid and Alcohol) • Hepatology • Non-alcoholic Steatohepatitis • CYP1A2 • CYP3A4

Preclinical evaluation of a protracted GLP-1/glucagon receptor co-agonist: Translational difficulties and pitfalls. (PubMed, PLoS One) - "In this paper, we present the pre-clinical evaluation of NN1177, a long-acting GLP-1/glucagon receptor co-agonist previously tested in clinical trials...To conclude, the pharmacodynamic effects at a given GLP-1-to-glucagon ratio differs between species, depends on compound exposure and study length, complicating the identification of an optimally balanced clinical candidate. The present findings could partly explain the low number of clinical successes for this dual agonism."

Journal • Preclinical • Obesity