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LY3463251

MARKETED

long-acting GDF15 receptor (GFRAL/RET) agonist

1
graded findings
1
effect domains
Evidence spread
High evidence 0Moderate evidence 0Low evidence 1Very low evidence 0

LY3463251 is shown as a marketed evidence record where applicable. Findings describe observed research and regulatory records; they do not provide treatment advice.

Thin or bounded evidence here means uncertainty remains visible. It is not evidence that an effect has been ruled out.
LY3463251 MARKETED
Pharmacology and mechanism Decrease
Low evidence

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