GLP-1 style drugs like Ozempic and Vegovy have become gamechangers in the fight against type 2 diabetes and reducing body fat, but for a significant portion of the population, the drugs have proven less successful. Some surprising new science suggests that this may be attributed to specific resistance to GLP-1s.
New Stanford Research Links Genetics to Ozempic and Vegov Response
new researchComing out of Stanford, and involving teams in England, Scotland and Australia, it has been found that genetic changes in the body can limit the ability of an enzyme called PAM, which has a role in activating hormones such as GLP-1. One of the symptoms of reduced effectiveness of the PAM enzyme is that the rate of gastric emptying does not slow down as expected. In mice with the same genetic variant, adding GLP-1 treatment failed to slow the passage of food through the stomach.
“Despite having higher circulating levels of GLP-1 in people with the PAM (limited) variant, we saw no evidence of higher biological activity,” Anna Gloyan explainedA professor of genetics who served as one of the study’s senior authors. “They were not lowering their blood sugar levels more quickly. More GLP-1 was required to have the same biological effect, meaning they were resistant to GLP-1.”
Why do some people lose weight on GLP-1 drugs?
With more than a quarter of patients with type 2 diabetes now taking GLP-1 medications, it is important to understand how and why 10% of these people may experience less effectiveness. “When I treat patients in the diabetes clinic, I see huge variation in response to these GLP-1-based drugs and it is difficult to predict this response clinically,” said Mahesh Umapathisivam, an endocrinologist at the University of Adelaide, who also served as fellow lead author. “This is the first step toward being able to use someone’s genetic makeup to help improve the decision-making process.”
Are new GLP-1 drugs being developed to overcome resistance?
While data shows that genetic differences may lead to resistance to GLP-1 and reduced ability to improve blood sugar levels, the actual results on weight loss are still being investigated. Still, this is an important development to ensure that these medications are effective for everyone. “There’s a whole class of drugs that are insulin sensitizers, so perhaps we can develop drugs that can sensitize people to GLP-1 or find formulations of GLP-1, like long-acting versions, that avoid GLP-1 resistance,” Goyne said.
