Activity of CYP3A4, a major drug-metabolizing enzyme, is reduced by 35% for several probes in obese individuals compared with their lean controls.8,9 A recent systematic review concluded that activity of CYP2C9, CYP1A2 and CYP3A4/5 is reduced in obese individuals, while CYP2E1 activity is enhanced.10 Furthermore, the chronic inflammation status linked to obesity may contribute to substantial alterations in drug-metabolizing enzymes and transporters,11 which adds another level of PK variability in subjects with obesity. This evidence concerns the gene CYP3A4 and obesity due to melanocortin 4 receptor deficiency.