Your Genes May Decide Whether GLP-1s Work—or Make You Sick

A new study finds specific genes can give weight loss drugs a boost, or make you feel ill.

BY MOSES JEANFRANCOIS, NEWS WRITER @MOSESJEANS

If the Ozempic isn’t working, it may be that your genes are to blame. A new study found that weight-loss drugs and GLP-1 rely heavily on genetics to get desired results. 

Mainstream GLP‑1 drugs, like Wegovy and Zepbound, cause weight loss by suppressing appetite, slowing gastric emptying, and changing brain signals related to hunger. Genetic differences, however, explain why some people lose a lot of weight, some lose a little, and some get more side effects. 

Published in the science journal Nature, the study covered more than 27,000 people who reported using GLP‑1 medications through 23andMe surveys and electronic health records. Those who had the GLP1R gene variant lucked out with greater weight loss. 

“Identifying factors that predict a person’s response to GLP1 medications may help guide treatment strategy,” reads the study. “These findings provide direct genetic evidence that variation in the drug target genes contributes to inter-person variability in response and lay the foundation for precision medicine approaches in the treatment of obesity.” 

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The findings look toward pharmacogenetics for obesity treatment, suggesting future GLP‑1 prescribing could be personalized based on genetic profiles.  

Researchers noted that two genes are in play: GLP1R, which is the primary gene linked to weight-loss response, and GIPR (glucose‑dependent insulinotropic polypeptide receptor), a side‑effect gene specific to tirzepatide. According to the study, both genes can come with variants that can help or hurt patients. 

In GLP1R, researchers identified a missense variant strongly associated with greater weight loss. Patients achieved about 0.7 to 0.8 kg more weight loss per copy of the variant, but also faced nausea and vomiting. 

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