First US-Based Trial of Mazdutide Finds Up to 18 Percent Weight Loss in Phase 2 Study Published in The Lancet Diabetes & Endocrinology

The Lancet Diabetes & Endocrinology published results online on August 21, 2026 from the first US-based clinical trial of mazdutide, a once-weekly GLP-1/glucagon dual receptor agonist, in adults with obesity or overweight. The randomized, double-blind, placebo-controlled phase 2 trial was conducted at 24 centers in the United States and funded by Eli Lilly and Company, which co-develops mazdutide with Innovent Biologics. The corresponding author was Olimpia Ferreira Galvao De Araujo of Eli Lilly.

Mazdutide is a synthetic analogue of the gut hormone oxyntomodulin that activates both the GLP-1 and glucagon receptors. It has previously been tested mainly in trials conducted in China, where it was approved by the National Medical Products Administration in 2025 for chronic weight management and, later, for glycemic control in type 2 diabetes. It is not approved by the FDA, the European Medicines Agency, or Australia's Therapeutic Goods Administration, where it remains investigational. The trial is registered on ClinicalTrials.gov as NCT06124807 and is listed as completed.

Between November 17, 2023 and July 9, 2025, investigators randomly allocated 179 adults aged 18 to 75 with a body mass index of 30 or higher, or 27 to under 30 with at least one weight-related complication, in a 3:2:3:3 ratio to receive once-weekly subcutaneous mazdutide at 3-6 mg (32 participants), 10 mg (48 participants), or 16 mg (51 participants), or placebo (48 participants), for 48 weeks. None of the participants had type 2 diabetes. The trial's primary endpoint was percentage change in bodyweight from baseline to 32 weeks.

At 32 weeks, the least-squares mean percentage change in bodyweight was -7.3% with the 3-6 mg dose, -15.6% with 10 mg, and -18.1% with 16 mg, compared with -0.9% with placebo. Estimated treatment differences versus placebo ranged from -6.5 to -17.2 percentage points, with all comparisons reaching statistical significance (p<0.0001). Additional weight reductions were observed by 48 weeks. The most common adverse events were gastrointestinal, mostly mild to moderate in severity, and discontinuation of study treatment due to adverse events occurred most often in the 16-mg group (20%), primarily linked to gastrointestinal disorders.

The study authors concluded that once-weekly mazdutide produced clinically meaningful bodyweight reduction across all doses tested in this US population, with higher doses producing greater weight loss. As a phase 2 trial without an active comparator, the results describe this specific 227-person study population and do not by themselves establish a US regulatory pathway. Mazdutide's approval in China does not extend to the United States, the European Union, or Australia, and this report describes trial findings rather than treatment or dosing guidance.