Hormonal
Tirzepatide induces significant weight reduction in individuals with obesity caused by pathogenic MC4R mutations, achieving efficacy comparable to non-carriers.
If you have obesity caused by an MC4R mutation, tirzepatide is a highly effective treatment option. Clinical data shows you will likely lose a significant amount of weight (around 18%) over 72 weeks, similar to people without this genetic mutation. Because lifestyle changes alone are often insufficient for this specific genetic profile, pharmacological intervention with tirzepatide is recommended to manage severe obesity and its complications.
In the treatment arm, the weight loss trajectory over 72 weeks was comparable in both groups: 18.3% weight reduction in MC4R mutation carriers versus 19.9% in noncarriers.
Why this rating
Retrospective analysis of a large, high-quality RCT (SURMOUNT-1) with genetic stratification, though the subgroup size (n=32) is small.
Source
Tirzepatide leads to weight reduction in people with obesity due to MC4R deficiency
Pallav Bhatnagar et al. · Nature Medicine · 2025
DOI 10.1038/s41591-025-03913-2
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