GLP-1-style drugs like Ozempic and Wegovy have been game-changers in the fight against type 2 diabetes and reducing body fat, but for a large portion of the population, the drugs have been less successful. This can be attributed to a specific resistance to GLP-1, which suggests some interesting science.
New Stanford research links genetics to Ozempic and Wegovy response
New researchwho came out of Stanford and involved teams from England, Scotland and Australia found that genetic variants in the body can limit the ability of an enzyme known as PAM, which has a role in activating hormones such as GLP-1. One of the signs of reduced effectiveness of PAM enzymes is that gastric emptying does not slow down as expected. In mice with the same genetic variant, the addition of GLP-1 treatments failed to slow the passage of food through the stomach.
“Although people with the PAM (restrictive) variant have higher circulating levels of GLP-1, we did not see any evidence of higher biological activity.” explained Anna Gloinprofessor of genetics, who was one of the main authors of the study. “They weren’t lowering their blood sugar as quickly. They needed more GLP-1 to have the same biological effect, meaning they were resistant to GLP-1.”
Why do some people lose less weight on GLP-1 pills?
While more than a quarter of patients with type 2 diabetes are now taking GLP-1 drugs, it is important to know how and why 10% of these people may 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 drugs, and it’s difficult to predict that response clinically,” said Mahesh Umapatisivam, an endocrinologist at the University of Adelaide who also served as lead author. “This is the first step to using someone’s genetic makeup to help us improve that decision-making process.”
Are new GLP-1 drugs being developed to overcome resistance?
Although data show that genetic differences can lead to resistance to GLP-1 and the ability to reduce blood sugar levels, the actual results of weight loss are still being investigated. However, this is an important step forward in making sure these drugs are effective for everyone. “There’s a whole class of drugs that are insulin sensitizers, so we can develop drugs that allow people to become sensitive to GLP-1 or find formulations of GLP-1, like long-acting versions, that avoid GLP-1 resistance,” Goin said.
