Innovent and Lilly's Mazdutide Outperforms Novo's Semaglutide in Head-to-Head Diabetes and Weight Loss Study

In a groundbreaking phase 3 study, Innovent Biologics and Eli Lilly's experimental GLP-1/glucagon (GCG) dual receptor agonist, mazdutide, has demonstrated superior efficacy compared to Novo Nordisk's established GLP-1 agonist, semaglutide, in both blood glucose control and weight loss metrics for patients with type 2 diabetes and obesity.

Study Design and Key Findings

The late-stage trial, conducted in China, enrolled 349 adults with early-stage type 2 diabetes and obesity who had inadequate glycemic and weight control after lifestyle intervention. Participants were randomized to receive either 6 mg of mazdutide or 1 mg of semaglutide.

The study's primary endpoint was the proportion of patients achieving both hemoglobin A1C (HbA1C) levels below 7.0% and body weight reduction of at least 10% from baseline at 32 weeks. Mazdutide significantly outperformed semaglutide, with 48% of patients in the mazdutide group meeting these benchmarks compared to 21% in the semaglutide group.

Further analysis revealed that mazdutide patients experienced:

• An average HbA1c reduction of 2.03%
• An average weight loss of 10.26% from baseline

In comparison, semaglutide patients showed:

• An average HbA1c reduction of 1.84%
• An average weight loss of 6% from baseline

Implications for Diabetes and Obesity Treatment

Dr. Linong Ji, the principal investigator of the trial, 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."

Mazdutide's dual-action mechanism, targeting both GLP-1 and GCG receptors, appears to offer enhanced benefits over single-target GLP-1 agonists like semaglutide. The GCG receptor activation is believed to increase energy expenditure and improve hepatic fat metabolism, potentially explaining the more pronounced weight loss effects observed in the study.

Regulatory Status and Future Directions

Mazdutide received its first-in-class approval from China's National Medical Products Administration (NMPA) in June for both weight management and type 2 diabetes. This milestone marks a significant advancement in incretin-based therapies.

Innovent and Lilly are not resting on their laurels, with plans to further investigate mazdutide's potential in:

• Adolescents with obesity
• Metabolic dysfunction-associated steatohepatitis (MASH)
• Certain heart failure indications
• Head-to-head comparison against Lilly's tirzepatide in obesity

Additionally, an ongoing study is comparing mazdutide and semaglutide in obesity accompanied by metabolic-associated fatty liver disease, further expanding the potential applications of this novel dual agonist.

As the pharmaceutical landscape continues to evolve, mazdutide's promising results may signal a shift in treatment paradigms for metabolic disorders, offering hope for improved outcomes in patients struggling with both diabetes and obesity.