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Monlunabant

MARKETED

peripherally-restricted CB1 receptor inverse agonist (non-incretin; obesity landscape contrast)

graded findings

effect domains

Evidence spread

High evidence 0Moderate evidence 2Low evidence 0Very low evidence 0

Monlunabant 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.

Monlunabant MARKETED

cns-neuropsychiatric Mixed

Moderate evidence

CB1 CONTRAST (non-incretin landscape context): monlunabant, a CB1 inverse agonist designed to be peripherally restricted, showed dose-dependent NEUROPSYCHIATRIC...

Knop FK et al., Lancet Diabetes Endocrinol, 2025 (monlunabant phase-2a, PMID 41038215); c... Source

Full findingCB1 CONTRAST (non-incretin landscape context): monlunabant, a CB1 inverse agonist designed to be peripherally restricted, showed dose-dependent NEUROPSYCHIATRIC adverse events in its phase-2a obesity trial, against the rimonabant precedent (CB1-antagonist depression/suicidality led to withdrawal). A preclinical study found monlunabant suppresses appetite via CENTRAL CB1 receptors, suggesting it is not fully peripherally confined and may carry rimonabant-like psychiatric risk. Decision-relevant CNS-safety contrast: CB1-antagonism carries a mechanism-specific neuropsychiatric liability the incretins do not appear to share.

PopulationMonlunabant phase-2a (NCT05891834): N=242 obesity + metabolic syndrome, 16 weeks, Canada; + a male-mouse central-mechanism study.

Fundingindustry-Novo Nordisk (Inversago Pharma)

Scope limitsconference/abstract-level; small sample (N~242)

Comparatorsplacebo

Thin or bounded evidence here means uncertainty remains visible. It is not evidence that an effect has been ruled out.

Monlunabant MARKETED

Weight change Decrease

Moderate evidence

In adults with obesity and metabolic syndrome, once-daily oral monlunabant 10 mg gave 7.1 kg weight loss vs 0.7 kg placebo at 16 weeks. Higher doses (20, 50 mg) showed...

Knop et al., Lancet Diabetes Endocrinol 2025; Novo Nordisk press 2024-09-20 Source

Full findingIn adults with obesity and metabolic syndrome, once-daily oral monlunabant 10 mg gave 7.1 kg weight loss vs 0.7 kg placebo at 16 weeks. Higher doses (20, 50 mg) showed dose-dependent withdrawals driven by neuropsychiatric/GI adverse events.

PopulationPhase 2a, N=243, 16 wk, randomised double-blind placebo-controlled dose-ranging (10/20/50 mg), 25 centres Canada; adults obesity + metabolic syndrome

Fundingindustry - Novo Nordisk (disclosed; amycretin)

Scope limitssmall sample (N~243)

Comparatorsplacebo