Semaglutide outpaced a rival

Weight-loss pills try to copy a gut hormone called glucagon-like peptide 1, which is one of the body’s “I’m full” signals after a meal. When that signal stays on longer, people usually eat less and lose weight over months, not days. (medicalnewstoday.com) For years, the strongest drugs in this class were mostly shots because protein drugs are hard to get through the stomach intact. The race now is to make pills that can get close to shot-like weight loss without a needle. (prnewswire.com) The two pills in this week’s comparison are built differently. Semaglutide is a peptide, which means a lab-made protein that mimics the natural hormone, while orforglipron is a small molecule, which means a simpler chemical compound designed to hit the same receptor. (prnewswire.com) Novo Nordisk presented new data on April 10 saying its once-daily semaglutide 25 milligram tablet beat Eli Lilly’s once-daily orforglipron 36 milligram tablet on average weight loss in adults with obesity or overweight. The result was shown at the Obesity Medicine Association annual meeting and reported the same day by Healio. (healio.com) This was not a trial where the two pills were handed to patients in the same study. It was an indirect comparison called ORION that matched people from Novo Nordisk’s OASIS 4 trial against people from Eli Lilly’s ATTAIN-1 trial and then adjusted for baseline differences. (prnewswire.com) In that ORION analysis, semaglutide 25 milligrams showed about 3 percentage points more mean body-weight reduction than orforglipron 36 milligrams. The reported differences were minus 3.2 percentage points under one analysis method and minus 3.0 percentage points under another, with confidence intervals that stayed below zero. (hcplive.com) The comparison also favored semaglutide on tolerability, which means how often people can stay on the drug without side effects forcing them off. Pharmacy Times reported higher odds of stopping orforglipron because of any adverse event and much higher odds of stopping because of stomach-related side effects in the cross-trial analysis. (pharmacytimes.com) The backdrop is that both pills have already put up meaningful numbers on their own. In OASIS 4, oral semaglutide 25 milligrams reached 16.6% average weight loss at 64 weeks if all participants stayed on treatment, while Novo Nordisk’s regulatory summary also reported 13.6% under the treatment-policy analysis that counts people whether or not they stopped. (novonordisk.mediaroom.com) Orforglipron has its own selling point: it does not come with food and water timing restrictions that have long been part of oral semaglutide use in diabetes. Eli Lilly has also said in a separate head-to-head diabetes trial that orforglipron beat lower-dose oral semaglutide on blood sugar and weight, which shows how much the answer can change when the dose and patient group change. (prnewswire.com) That is why this week’s result is a clue, not a final verdict. ORION compares one company’s 64-week obesity study with another company’s obesity study rather than randomizing the same patients side by side, so a true head-to-head obesity trial would carry more weight than this matched analysis. (healio.com)