Innovent and Lilly's Mazdutide Outperforms Novo's Semaglutide in Landmark Head-to-Head Study

In a groundbreaking development for the pharmaceutical industry, Innovent Biologics and Eli Lilly's experimental GLP-1/glucagon (GCG) dual receptor agonist, mazdutide, has demonstrated superior efficacy compared to Novo Nordisk's leading GLP-1 agonist, semaglutide, in a phase 3 head-to-head trial. The study, which focused on patients with early-stage type 2 diabetes (T2D) and obesity, marks a significant milestone in the ongoing competition for dominance in the rapidly expanding market for incretin-based therapies.

Study Results Highlight Mazdutide's Broader Effects

The late-stage trial, conducted in China, evaluated mazdutide against semaglutide across both blood sugar control and weight loss metrics. Innovent reported that 48% of patients in the mazdutide group achieved the primary endpoint—a combination of hemoglobin A1C (HbA1C) levels below 7.0% and body weight reduction of at least 10% from baseline at 32 weeks. In comparison, only 21% of patients in the semaglutide arm met these criteria.

Mazdutide demonstrated superior performance in individual metrics as well:

• HbA1c reduction: 2.03% (mazdutide) vs. 1.84% (semaglutide)
• Average weight loss: 10.26% (mazdutide) vs. 6% (semaglutide)

Principal investigator Linong Ji, M.D., emphasized the importance of these findings, stating, "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."

Implications for the Incretin Therapy Landscape

The success of mazdutide in this head-to-head comparison could potentially reshape the competitive landscape for incretin-based therapies. As the world's first approved GLP-1/GCG dual receptor agonist, mazdutide represents a new class of medications that may offer broader benefits to patients requiring improvements in glycemic control, body weight, and cardiometabolic risk factors.

Innovent's chief R&D officer of general biomedicine, Lei Qian, M.D., Ph.D., highlighted the drug's potential to benefit "a wide range of patients requiring multifaceted improvements in glycemic control, body weight, and cardiometabolic risk factors."

Mazdutide received its first-in-class approval from China's National Medical Products Administration (NMPA) in June, marking a significant milestone for incretin medicines. The drug's unique mechanism of action, which targets both GLP-1 and GCG receptors, is believed to increase energy expenditure and improve hepatic fat metabolism, potentially offering enhanced weight loss benefits when combined with the insulin-related advantages of GLP-1 agonists.

While mazdutide has gained approval in China for both weight management and type 2 diabetes, Eli Lilly retains the rights to the drug outside of China, where it has yet to secure regulatory approval. The ongoing collaboration between Innovent and Lilly, which began in 2019, underscores the strategic importance of this novel therapy in the global pharmaceutical landscape.

As the industry awaits further developments, Innovent has announced plans for additional studies comparing mazdutide to other leading treatments, including a head-to-head trial against Lilly's tirzepatide in obesity. These ongoing investigations, along with planned studies in adolescents with obesity, metabolic dysfunction-associated steatohepatitis (MASH), and certain heart failure indications, suggest that the full potential of mazdutide is yet to be fully explored.