Your Genes May Predict How Your Body Reacts To GLP-1s, New Study Says

If you've ever scrolled through social media and wonder why everyone else seems to be losing 40 pounds on GLP-1s while you're struggling to see a difference, you're not imagining things. The difference might actually be written in your DNA.

Researchers at 23andMe surveyed nearly 28,000 people taking GLP-1 medications and conducted a study to identify genetic factors linked to treatment response. The participants were mostly female (82.4%), with a median age of 52, and had been on their medication for a median of 8.3 months. Participants lost about 25 pounds on average, which amounts to approximately 11.7% of their pre-treatment weight.

Most notably, the researchers identified a specific variant in the GLP1R gene (the gene that encodes the receptor these drugs target) that was associated with greater weight loss.

People who carried this variant (called rs10305420) lost an additional 1.67 lbs per copy of the variant allele. The finding was significant enough to replicate in a separate cohort of 4,855 people from the All of Us research program, which gives research confidence this genetic link is legitimate.

If you've experienced nausea or vomiting on a GLP-1 medication, you might have wondered if it means the drug is "working." According to this research, there may be some truth to this theory.

The same GLP1R varaint linked to greater weight loss was also associated with a higher likelihood of experiencing nausea and vomiting. The researchers found that these signals likely share the same underlying genetic cause, suggesting that side effects and efficacy may be biologically connected.

For people taking tirzepatide specifically, there's another gene in play: GIPR. Tirzepatide is a dual agonist, meaning it targets both the GLP-1 and GIP receptors. The study identified a variant in the GIPR gene (rs1800437) that was linked to vomiting risk, but only in tirzepatide users, not those on semaglutide. People who carried the genetic varaints at both the GLP1R and GIPR genes had a 14.8-fold increased odds of experiencing vomiting on tirzepatide compared to those without these variants.

Genetics isn't the whole story. The researchers also built models incorporating non-genetic factors and found that variables like sex, drug type, dosage, and time on treatment explained about 21% of the variance in weight loss.

This research lays the groundwork for what scientists call pharmacogenetics, a field where doctors examine your genetic profile to predict how you'll respond to a medication before you even start taking it.

While genetic testing for GLP-1 response isn't clinically available yet, these findings suggest it could be on the horizon. This means people may be able to know ahead of time whether they're likely to respond well to semaglutide, or whether tirzepatide might come with a higher risk of nausea.

For now, the study reinforces what many people on these medications already sense: individual response varies widely. Plus, this variation isn't random: it's at least partly biological.