Genetic Variants Reduce GLP-1 Drug Effectiveness in 10% of Diabetes Patients

New research has uncovered genetic variants that reduce the effectiveness of popular GLP-1 receptor agonist drugs, such as Ozempic and Wegovy, in controlling blood sugar for about 10 percent of people with type 2 diabetes. The study, published this month in Genome Medicine, highlights how these variants lead to a condition known as GLP-1 resistance, prompting calls for more personalized treatment approaches.

GLP-1 drugs mimic a natural hormone called glucagon-like peptide-1, which helps regulate blood sugar by stimulating insulin release, slowing stomach emptying and curbing appetite. Widely prescribed for type 2 diabetes and weight management, the medications are used by more than a quarter of diabetes patients. However, responses vary, with some individuals seeing minimal benefits despite consistent use.

The international team of researchers, including scientists from Stanford University, the University of Oxford and ETH Zurich, focused on variants in the PAM gene, which encodes an enzyme essential for activating hormones like GLP-1 through a process called amidation. These variants, present in roughly 10 percent of the general population and more common among those with...