GLP-1 style drugs like Ozempic and Wegovy have become a gamechanger in the fight against type 2 diabetes and lowering body fat, but for a significant portion of the population, the drugs have proved to be less successful. This could be attributed to specific resistance to GLP-1s, suggests some startling new science.
New Stanford Research Links Genetics to Ozempic and Wegovy Response
The new research, coming out of Stanford, and involving teams from England, Scotland, and Australia, has found that genetic variants in the body may limit the ability of an enzyme known as PAM, which has the role of activating hormones such as GLP-1. One of the symptoms of reducing the effectiveness of the PAM enzyme is that gastric emptying is not slowed down as expected. In mice with the same genetic variants, the addition of GLP-1 treatments failed to slow the passage of food through the stomach.
“Despite people with the PAM (limiting) variant having higher circulating levels of GLP-1, we saw no evidence of higher biological activity,” explained Anna Gloyn, a professor of genetics who served as one of the study’s senior authors. “They were not reducing their blood sugar levels more quickly. More GLP-1 was needed to have the same biological effect, meaning they were resistant to GLP-1.”
Why Some People Lose Less Weight on GLP-1 Medications
With more than a quarter of type 2 diabetes patients now taking GLP-1 drugs, it is important to know how and why 10% of these people could have a less effective experience. “When I treat patients in the diabetes clinic, I see a huge variation in response to these GLP-1-based medications and it is difficult to predict this response clinically,” said Mahesh Umapathysivam, an endocrinologist from Adelaide University, who also served as a fellow lead author. “This is the first step in being able to use someone’s genetic make-up to help us improve that decision-making process.”
Are New GLP-1 Drugs Being Developed to Overcome Resistance?
While the data illustrates that genetic differences can lead to a resistance to GLP-1 and a lessened ability to improve blood sugar levels, the actual results on weight loss is still being investigated. Still, this is an important development for making sure these drugs are effective for all. “There are a whole class of medications that are insulin sensitizers, so perhaps we can develop medications that will allow people to be sensitized to GLP-1s or find formulations of GLP-1, like the longer-acting versions, that avoid the GLP-1 resistance,” said Goyne.
