Uneven weight loss on GLP-1 drugs now has a concrete suspect: genetics. A new study reports that two genes involved in gut hormone pathways may shape how strongly people respond to these widely used obesity and diabetes treatments.

Researchers focused on genes that influence secretion and signaling of glucagon-like peptide-1 and related incretin hormones, which help regulate appetite, gastric emptying, and insulin release. Variants in these genes appear to alter receptor sensitivity and downstream signal transduction, changing how brain centers that govern satiety interpret the same drug dose. In effect, the pharmacodynamics of GLP-1 agonists may depend on a person’s inherited wiring, not just on dosage or baseline metabolic rate.

The work adds mechanistic weight to the idea of pharmacogenomics for obesity care, in which treatment choice and dose are tailored to each patient’s molecular profile. It also helps explain why some individuals see dramatic reductions in body mass while others plateau despite adherence. As GLP-1 drugs reshape the market for metabolic therapies, the next competitive edge may lie in pairing them with routine genetic screening, turning a blunt tool into a more discriminating instrument.