Safety and genetics in GLP‑1 responses

Glucagon-like peptide 1 drugs change appetite and blood sugar, but two new studies suggest the effects are not the same for every patient. One study found no higher eye-nerve risk with semaglutide in obesity, while another linked genetic variants to differences in weight loss and side effects. (healio.com) (nature.com) The eye condition is non-arteritic anterior ischemic optic neuropathy, a rare loss of blood flow to the optic nerve that can damage vision. At the American College of Physicians Internal Medicine Meeting in San Diego, researchers reported semaglutide was not associated with higher odds of that complication in adults with overweight or obesity. (healio.com) In the same analysis, semaglutide was linked to lower odds of non-arteritic anterior ischemic optic neuropathy in patients with type 2 diabetes, with an odds ratio of 0.36 and a 95% confidence interval of 0.25 to 0.51. The study used Military Health System Data Repository records for 1,212,775 adults treated between December 7, 2017, and September 30, 2023. (healio.com) Those results land after smaller and more selective studies pointed the other way. A 2024 JAMA Ophthalmology study of 16,827 patients found higher risk in matched semaglutide cohorts, and a 2026 Danish cohort study reported a doubling of five-year risk in people with type 2 diabetes. (jamanetwork.com) (aaojournal.org) The newer military-database study also came with limits. The researchers said claims data can include coding errors and cannot confirm whether patients actually took the drug or whether every diagnosis was clinically verified. (healio.com) A separate paper in Nature looked at why some people lose much more weight on these drugs than others. Researchers analyzed self-reported outcomes from 27,885 users of glucagon-like peptide 1 medicines and found a variant in GLP1R, the gene for the drug target, associated with an extra 0.76 kilograms of weight loss per copy of the effect allele. (nature.com) The same study linked variation in GLP1R and GIPR to nausea or vomiting on treatment. The GIPR signal appeared only in people taking tirzepatide, not semaglutide, according to the paper and a 23andMe Research Institute summary released April 8, 2026. (nature.com) (23andme.com) The 23andMe team said some users lose less than 5% of body weight on these medicines, while others lose more than 20%, and some develop nausea and vomiting while others do not. The researchers said their model combined genetic, demographic, and clinical factors to sort patients by likely benefit and side-effect risk. (23andme.com) (nature.com) Taken together, the two reports add detail to a fast-moving question around obesity drugs: who benefits most, who feels the worst side effects, and which safety signals hold up in larger datasets. For now, the picture is more specific than simple, with one rare eye-risk signal still debated and patient-to-patient differences increasingly measurable. (healio.com) (nature.com)