Mazdutide beats semaglutide on blood sugar and weight in first head-to-head Phase 3

Innovent Biologics said mazdutide, an experimental GLP-1/glucagon dual agonist it is developing with Eli Lilly, outperformed semaglutide on both blood sugar and weight loss in a Phase 3 trial — the first head-to-head study to compare a drug from the GLP-1/glucagon class with semaglutide ^[1].

The Suzhou-based company announced the results in an Oct. 26 press release ^[1]. Novo Nordisk markets semaglutide as injectable Ozempic and oral Rybelsus for type 2 diabetes and as Wegovy for obesity ^[1].

What the trial found

The China-only study enrolled 349 adults with early-stage type 2 diabetes and obesity who had inadequate blood sugar and weight control after lifestyle changes, with or without standard metformin monotherapy ^[1]. Patients received either a 6-mg dose of mazdutide or a 1-mg semaglutide regimen ^[1].

The trial's primary endpoint looked at the share of patients who met a combined blood sugar and weight goal at 32 weeks — including a body weight reduction of at least 10% from baseline ^[1]. About 48% of patients in the mazdutide group met the benchmark, compared with 21% in the semaglutide group ^[1].

On the individual measures, mazdutide lowered HbA1c by 2.03 percentage points on average versus 1.84 points for semaglutide, and produced average weight loss of 10.26% versus 6% ^[1].

"Treatment strategies that address both glycemic control and weight loss are playing an increasingly critical role in improving clinical outcomes for patients with T2D and comorbid obesity," principal trial investigator Linong Ji, M.D., said in the release ^[1]. Innovent's chief R&D officer of general biomedicine, Lei Qian, M.D., Ph.D., said the drug may benefit "a wide range of patients requiring multifaceted improvements in glycemic control, body weight, and cardiometabolic risk factors" ^[1].

Mazdutide won approval from China's National Medical Products Administration in June for weight management and type 2 diabetes, making it the first approved GLP-1/GCG drug ^[1]. Under a 2019 agreement, Lilly holds rights to mazdutide outside China, where it has not been approved ^[1].

Why it matters for patients

Mazdutide is not available in the United States, and no US approval timeline has been disclosed ^[1]. For people currently taking Ozempic, Wegovy, Rybelsus or another GLP-1, the result does not change what is on the market or what insurers cover.

The findings come from a single trial of 349 people in China, run for 32 weeks ^[1]. Whether the same advantage would show up in a larger, more diverse US population has not been established. The trial also tested one specific pairing — 6 mg of mazdutide against a 1-mg semaglutide regimen ^[1]. Whether the results would hold against higher semaglutide doses used for obesity treatment has not been reported. Safety and side-effect data from the trial were not included in the announcement ^[1].

If mazdutide eventually reaches the US market, it would add another option in a field where patients and doctors already weigh blood sugar control against weight loss and tolerability. Nothing in this trial speaks to how mazdutide compares with tirzepatide, the molecule in Mounjaro and Zepbound, in a head-to-head setting ^[1].

What happens next

Mazdutide and semaglutide are also going head-to-head in an ongoing study in obesity with metabolic-associated fatty liver disease ^[1]. Innovent said it plans further studies of mazdutide in adolescents with obesity, in metabolic dysfunction-associated steatohepatitis (MASH), in certain heart failure indications, and against Lilly's tirzepatide in obesity ^[1]. No dates or timelines for those studies were disclosed ^[1].