The Genetics of GLP-1s: Why Two People on the Same Dose Get Different Results
Darren W. Dubyak
Founder and Clinical Director of Body by AIM360®
7 hours ago
- Which medication, not just whether to medicate, may be a genetic question. The GLP1R gene encodes the receptor semaglutide binds to, so a less functional receptor means the drug has less to work with. Tirzepatide adds a second target, GIPR, and variants there shape how well that second mechanism lands. Dr. Gibson’s point is that most prescribing today is driven by availability and insurance when the panel may have something useful to say first.
- “GLP-1 medications don’t selectively burn fat.” I asked Dr. Gibson to say that twice because people still don’t believe it. Research shows a meaningful share of the weight lost on these medications is lean mass, and it gets worse without deliberate protein intake and resistance training. Variants in TRHR and IGF2 influence how well someone holds onto muscle in a caloric deficit, which is a conversation that belongs before the first injection, not after.
- The rebound after stopping is biology snapping back, not weakness. If FTO, the leptin receptor, or HTR2C are working against you, the medication compensates for those variants, it doesn’t correct them. The people carrying the heaviest satiety burden are the ones most dependent on the drug to feel full at all, and therefore the ones facing the steepest rebound risk. Which is exactly why the real protocol gets built during the medication window, not after it closes.
Comments