Genetics may personalise GLP‑1 use

Glucagon-like peptide 1 is a gut hormone your body releases after you eat, and obesity drugs such as semaglutide copy that signal to slow stomach emptying and reduce appetite. Tirzepatide goes one step further by also copying gastric inhibitory polypeptide, a second meal signal that acts on a different receptor. (nature.com) Those drugs can look almost magical in one patient and frustrating in another. In the new Nature study, some users lost less than 5% of body weight while others lost more than 20%, even though they were taking medicines from the same family. (news-medical.net) The reason scientists went looking in DNA is simple: receptors are the locks, and these drugs are the keys. If the lock is built a little differently from birth, the same key can open it more strongly, more weakly, or with more side effects. (nature.com) Researchers at 23andMe tested that idea in 27,885 people who reported using glucagon-like peptide 1 receptor agonist drugs. They scanned the genome for common variants linked to weight loss and to nausea or vomiting during treatment. (nature.com) They found one protein-changing variant in the glucagon-like peptide 1 receptor gene, called GLP1R, that was tied to better weight loss. Each copy of that variant was linked to about 0.76 kilograms of extra weight loss on treatment. (nature.com) They also found that nausea and vomiting were not random bad luck. Variants in GLP1R and in the gastric inhibitory polypeptide receptor gene, called GIPR, were linked to those stomach side effects. (nature.com) One detail stood out because it matched how the drugs work. The GIPR side-effect signal showed up only in people taking tirzepatide, which targets both the glucagon-like peptide 1 receptor and the gastric inhibitory polypeptide receptor, and not in people taking semaglutide, which targets only the glucagon-like peptide 1 receptor. (nature.com) This does not mean a cheek swab will decide your prescription next week. The paper says the genetics can stratify patients by likely benefit and side-effect risk, but the model still needs to be turned into a clinical tool doctors can actually use. (nature.com) (news-medical.net) The commercial angle is obvious because these medicines already compete on small differences in results, tolerability, and convenience. Eli Lilly just won United States approval for its oral obesity pill, orforglipron, branded Foundayo, adding a new front to its fight with Novo Nordisk’s Wegovy franchise. (statnews.com) (biopharmadive.com) Investors are already talking as if Lilly has momentum. Reuters reported on April 2 that analysts expect Lilly’s new pill to generate billions in sales quickly, while 24/7 Wall St. argued on April 10 that Lilly is pulling ahead on efficacy and manufacturing scale. (finance.yahoo.com) (247wallst.com) If DNA can tell a doctor that one patient is more likely to lose weight on semaglutide and another is more likely to tolerate tirzepatide, the drug race stops being only about who has the strongest brand. It becomes a race to match the right molecule to the right body before the first prescription is written. (nature.com)