LY3463251
MARKETED
Proof-of-mechanism: in overweight/obese participants, 12-week multiple-ascending-dose LY3463251 significantly reduced food intake and appetite scores independent of...
Benichou et al., Cell Metab 2023 (LY3463251 discovery and clinical proof of mechanism)
Source
Full findingProof-of-mechanism: in overweight/obese participants, 12-week multiple-ascending-dose LY3463251 significantly reduced food intake and appetite scores independent of nausea/emesis, but produced only modest body-weight reduction. The GDF15 axis suppresses appetite without the expected weight magnitude, a challenge for clinical weight-loss use.
PopulationPhase 1 multiple-ascending-dose, 12 weeks, healthy and overweight/obese participants, placebo-controlled
Fundingindustry - Eli Lilly (trial sponsor; inferred from registration trial)
Scope limitsMechanism: agonist at GFRAL/RET (the GDF15 receptor complex restricted to area postrema/NTS), suppressing appetite via a non-incretin brainstem pathway. Eli Lilly. Co-occurs in incretin comparisons as the canonical GDF15/GFRAL mechanism and a contrast case (appetite suppression without proportional weight loss).
Comparatorsplacebo