About 10% may be GLP‑1 resistant

Glucagon-like peptide-1 is a gut hormone that helps the body release insulin after meals, and drugs like Ozempic and Wegovy are built to copy that signal. A Stanford Medicine team now says about 1 in 10 people may carry gene variants that blunt that response. (med.stanford.edu) The Stanford group reported the finding on April 10, 2026, and said the work was published the same day in *Genome Medicine* after a decade-long international project using human studies, mouse experiments, and diabetes drug trial data. The researchers said the variants are carried by roughly 10% of the general population. (med.stanford.edu; sciencedaily.com) The basic idea is simple: some people appear to make higher levels of natural glucagon-like peptide-1, but the hormone is less biologically effective. The researchers call that pattern “glucagon-like peptide-1 resistance.” (med.stanford.edu) In several clinical trials, people with those variants lowered blood glucose less effectively after six months on glucagon-like peptide-1 receptor agonists, according to senior author Anna Gloyn of Stanford. The study focused on blood-sugar control in Type 2 diabetes, not on weight-loss results. (med.stanford.edu) That distinction matters because semaglutide drugs such as Ozempic and Wegovy are used at different doses for diabetes and obesity. Stanford said it is still not clear whether the same variants also reduce weight loss from those medicines. (med.stanford.edu) The lead author, Mahesh Umapathysivam of Adelaide University, said doctors already see “huge variation” in how patients respond to these drugs. Stanford said a genetic test could eventually help move patients to a better treatment faster, instead of waiting months to see whether blood sugar improves. (med.stanford.edu) A separate paper in *Nature*, published April 8, 2026, reached a related conclusion from the weight-loss side: genes tied to glucagon-like peptide-1 receptor and glucose-dependent insulinotropic polypeptide receptor help explain differences in both efficacy and side effects. That study analyzed 27,885 people using glucagon-like peptide-1 medications and found one receptor variant linked to an extra 0.76 kilograms of weight loss per copy of the effect allele. (nature.com) Together, the two studies point in the same direction: response to these medicines is not uniform, and part of that variation appears to be inherited. Stanford said the “million-dollar question” is still the mechanism, which means the genetics are clearer than the biology for now. (med.stanford.edu; nature.com)