Hormonal
Pharmacological inhibition or genetic deletion of the melanocortin-3 receptor (MC3R) enhances the anorectic and weight-loss efficacy of GLP-1 receptor agonists (e.g., liraglutide, semaglutide, tirzepatide) without increasing malaise or peripheral incretin effects.
Current research indicates that blocking the MC3R receptor can make GLP-1 weight loss drugs (like Ozempic or Wegovy) work better, allowing for lower doses to achieve the same weight loss. This happens without increasing the nausea or stomach upset often associated with these drugs. However, effective MC3R-blocking drugs that can cross into the brain are not yet widely available for human use.
Our findings reveal that genetic deletion or pharmacological inhibition of MC3R improves the dose responsiveness to Glucagon-like peptide 1 (GLP1) agonists, as assayed by inhibition of food intake and weight loss.
Why this rating
Strong preclinical evidence in mice with clear dose-response curves and specificity controls, but lacks human clinical data.
Source
Inhibition of the melanocortin-3 receptor (MC3R) causes generalized sensitization to anorectic agents
Naima S. Dahir et al. · bioRxiv (Cold Spring Harbor Laboratory) · 2023
DOI 10.1101/2023.12.05.570114
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