Experimental Add-On Drug Boosted Weight Loss In Diabetes Patients On Dulaglutide

Researchers tested nisotirostide, a new drug that activates the NPY2 receptor, a hormone-signaling target different from the GLP-1 receptor used by drugs like semaglutide and dulaglutide. In mouse studies, nisotirostide alone reduced body weight by up to 12%; combined with a GLP-1 drug, mice lost up to 31% of body weight, which the study authors describe as a synergistic effect. The Phase 1 human trial enrolled 65 healthy participants and participants with type 2 diabetes already taking a 1.5 mg weekly dose of dulaglutide. Participants received a single injection of nisotirostide at doses ranging from 0.025 mg to 1 mg. At the 1 mg dose, nisotirostide alone reduced body weight by 0.75 kg versus placebo, a difference the study did not report as statistically meaningful. When added to dulaglutide, nisotirostide produced up to 2.58 kg more weight loss than dulaglutide alone, which did reach statistical significance. The drug's pharmacokinetics, how the body absorbs and clears it, supported once-weekly dosing. Gastrointestinal side effects, including nausea and vomiting, were the most commonly reported adverse events, and the study authors note these were dose-dependent and mild to moderate in severity.