A phase 3 clinical trial found that the dual GLP-1 and glucagon receptor agonist mazdutide led to substantial weight loss and improvements in cardiometabolic markers among Chinese adults with obesity, according to a report published on June 9. The study also noted gastrointestinal side effects that clinicians will need to address.
Researchers conducted the GLORY-2 clinical trial from December 2023 to November 2025 across 27 hospitals in China, focusing on adults with a body mass index of at least 30. Participants were randomized in a two-to-one ratio to receive either a weekly nine-milligram dose of mazdutide or placebo, alongside diet and exercise recommendations. The primary analysis included 461 participants, of whom approximately sixteen percent had both obesity and type 2 diabetes.
The results showed that those receiving mazdutide experienced an average body weight reduction of sixteen point six five percent over sixty weeks, compared to one point five percent for the placebo group. Eighty-four point three percent of participants taking mazdutide lost at least five percent of their body weight versus thirty-three point one percent in the placebo group. Secondary analyses revealed similar trends for greater thresholds of weight loss, including ten, fifteen, and twenty percent reductions.
In addition to weight changes, participants who received mazdutide saw improvements in waist circumference—an average decrease of twelve point eight two centimeters compared with two centimeters for placebo—as well as reductions in systolic blood pressure and cholesterol levels. However, more than half reported vomiting during treatment; nausea and diarrhea were also common but mostly mild or moderate and occurred primarily during initial dose escalation.
The study reported no deaths but noted some adverse events such as transient heart rate increases, cases of acute gallbladder disease, papillary thyroid cancer diagnoses within the active drug group, and no cases of acute pancreatitis. Researchers acknowledged limitations including lack of comparison with lower doses and limited data regarding patients with type 2 diabetes or other ethnicities outside China.
Authors concluded that tailored dosing schedules may help manage early gastrointestinal side effects if this dual agonist is adopted into clinical practice.
