Nature paper finds genetic variants that predict GLP-1 weight loss response
Posted by weekendnate in Weight Loss & Metabolic - 1 points, 4 comments.
Nature just put out a study identifying genetic predictors for how people respond to GLP-1 agonists, both for weight loss and side effects. They used longitudinal EHR data and found reduced effects in certain ancestry groups, which lines up with what a lot of us have seen anecdotally where some folks are super responders and others stall hard no matter what they do.
The ancestry angle is what gets me. Most of the trial data we have is from middle and high income countries, so the fact that response varies by genetic background has always been a blind spot. If this holds up in replication, it could actually explain a chunk of the "I'm eating 1200 calories and the scale won't move" posts we see.
For those of you who have run longer protocols, did your best responders and worst responders cluster in any obvious way? Or did it feel totally random?
Comments
- quiet_ironman: Honestly this is exciting but I wanna pump the brakes a little 🔬 the ancestry piece is huge, like the OP said, most trial data skews white and wealthy so we have been flying blind on a lot of this. What I keep wondering is whether the "responder vs not" thing is actually genetics at all or whether it is stuff like starting metabolic health, how long someone was insulin resistant before they started, sleep, muscle mass. Like all the usual suspects. The super responders I have seen in my own ci
- weekendnate: Yeah, that's fair, and honestly it's probably both. The paper didn't claim genetics was the whole story, just that it explains some of the variance on top of everything else. Duration of insulin resistance before starting is something I keep coming back to in my own data too, the people who started earlier seem to respond more cleanly.
- elle_z: This is a Those confounders are so hard to untangle from genetics in the data too, like if someone was metabolically healthier to begin with they probably also had more energy to make the lifestyle changes at the same time. Hard to know which one actually moved the needle. Do you think the study tried to adjust for any of that or was it mostly just the genetic variants they were looking at?
- weekendnate: Honestly not sure, I only skimmed the methods section. But they pulled from EHR data which usually has decent metabolic markers (A1c, lipids, BMI trajectory) so I'd hope they at least controlled for starting metabolic health, but yeah the lifestyle confound is real. Hard to capture diet quality or activity from a chart note. If anyone has dug into the supplement on this I'd love to know how deep they went with the covariates.
Community discussion - research and educational context only. Not medical advice.