Mazdutide beats semaglutide in the first head-to-head Phase 3 of a GLP-1/glucagon agonist

Mazdutide, an experimental GLP-1/glucagon dual receptor agonist developed by Innovent Biologics and Eli Lilly, outperformed Novo Nordisk's semaglutide in a Chinese Phase 3 trial that compared the two drugs directly for the first time.^[1] The results, announced October 26 in a press release, cover both blood sugar control and weight loss in people with type 2 diabetes and obesity.^[1]

The trial, called DREAMS-3, enrolled 349 adults in China with early-stage type 2 diabetes and obesity who had not reached target blood sugar or weight goals through lifestyle changes alone, whether or not they were also taking metformin.^[1] Researchers compared a 6-mg dose of mazdutide against a 1-mg dose of semaglutide, which Novo Nordisk sells as Ozempic and Rybelsus for diabetes and as Wegovy for weight management.^[1]

At 32 weeks, 48% of patients on mazdutide reached both study targets — an A1C under 7.0% and at least 10% body weight loss from baseline — compared with 21% of patients on semaglutide.^[1] Looking at each measure separately, mazdutide lowered A1C by an average of 2.03 percentage points and cut body weight by an average of 10.26%, versus a 1.84 percentage point A1C drop and 6% weight loss for semaglutide.^[1]

Mazdutide works by targeting both the GLP-1 receptor, which affects insulin and appetite, and the glucagon receptor, which can raise energy expenditure and improve how the liver processes fat.^[1] Innovent says this combined mechanism may explain the added weight loss and blood sugar benefit seen in the trial. The drug won approval in China in June for weight management and type 2 diabetes, the first approval anywhere for a GLP-1/glucagon combination.^[1] Eli Lilly holds rights to mazdutide outside China but has not yet won approval for it in the United States or elsewhere.^[1]

Why it matters for patients

This is the first head-to-head Phase 3 trial pitting a GLP-1/glucagon drug against semaglutide, so it gives an early signal about how a newer class of incretin medicines might compare with a drug many US patients already know as Ozempic, Wegovy, or Rybelsus.^[1] The trial was conducted only in China, using Chinese participants and a China-only regulatory context, so it is not yet known how these results would translate to a US population or to head-to-head comparisons with US-marketed doses.^[1]

For patients in the United States thinking about GLP-1 treatment, mazdutide is not an option right now. It has not been approved by US regulators, and the sources do not say when or whether Lilly plans to seek US approval.^[1] Patients currently using semaglutide products should know these results reflect one specific trial design, dose comparison, and population, not a broad statement about semaglutide's effectiveness across all uses or doses.^[1]

The trial also compared a specific 6-mg mazdutide dose against a 1-mg semaglutide dose, and the sources do not explain how these doses were chosen relative to what is typically prescribed in the US for weight loss or diabetes, an important detail for interpreting the size of the reported differences.^[1]

What happens next

Innovent says it is already running another trial comparing mazdutide and semaglutide in patients with obesity and a related fatty liver condition, though no results or dates were given.^[1] The company also plans further studies of mazdutide in adolescents with obesity, in a liver disease called MASH, in certain heart failure patients, and in a future head-to-head comparison against Lilly's tirzepatide, sold in the US as Mounjaro and Zepbound, for obesity.^[1] No timeline or expected results were disclosed for these planned studies, and no US regulatory filing or approval timeline for mazdutide has been announced.^[1]