An experimental GLP-1/glucagon (GCP) dual receptor agonist from Eli Lilly and its Chinese partner, Innovent, has bested Novo Nordisk’s reigning GLP-1 semaglutide, in a phase 3 study across both blood sugar and weight loss metrics. 

The late-stage trial evaluating mazdutide, the world’s first approved GLP-1/GCG, is also the first to pit a drug from the class against semaglutide in a head-to-head comparison, the Suzhou-based drugmaker said in an Oct. 26 press release.

Novo markets its semaglutide as injectable Ozempic and oral Rybelsus for type 2 diabetes and as Wegovy for obesity.

Innovent pitted a 6-mg dose of mazdutide against a 1-mg semaglutide regimen in its study of 349 Chinese adults with early-stage type 2 diabetes (T2D) and obesity. To qualify for the China-only trial, patients had to have inadequate glycemic and weight control after lifestyle intervention, regardless of whether they were taking standard metformin monotherapy.

Mazdutide's performance against Novo's semaglutide allowed the trial to meet its primary endpoint, which looked at the proportion of patients who achieved hemoglobin A1C (HbA1C) or blood glucose levels over 7.0%, as well as body weight reduction of at least 10% from baseline at the study's 32-week mark. 

Some 48% of patients in the trial's mazdutide group met those blood sugar and weight loss benchmarks, compared to 21% in the semaglutide arm, Innovent said.

Mazdutide also had an apparent edge over semaglutide on both blood glucose levels and weight loss separately, helping patients lower their HbA1c by 2.03% and lose 10.26% of their weight from baseline on average. Semaglutide, meanwhile, triggered a 1.84% reduction in HbA1c levels and helped patients achieve an average 6% weight loss.

“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., explained in the release.

Mazdutide, approved in China for weight management and type 2 diabetes, may benefit “a wide range of patients requiring multifaceted 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., added. 

The drug won its first-in-class approval from China’s National Medical Products Administration (NMPA) in June, marking a breakthrough moment for incretin medicines. Targeting the GCG receptor can increase the body’s energy expenditure and improve hepatic fat metabolism, creating a powerful weight loss mechanism when added to the insulin benefits of GLP-1 agonists.

Innovent signed a 2019 agreement with Lilly to license the drug in China, marking an extension of a decade-long partnership between the two companies. Lilly maintains the rights to the mazdutide outside of China, where it has yet to win approval.

Mazdutide and semaglutide are also going head-to-head in another ongoing study that compares the medications in obesity accompanied metabolic-associated fatty liver disease. Innovent is planning to further study mazdutide in adolescents with obesity, metabolic dysfunction–associated steatohepatitis (MASH), certain heart failure indications and against Lilly’s tirzepatide in obesity. 

An experimental GLP-1/glucagon (GCP) dual receptor agonist from Eli Lilly and its Chinese partner, Innovent, has bested Novo Nordisk’s reigning GLP-1 semaglutide, in a phase 3 study across both blood sugar and weight loss metrics. 

The late-stage trial evaluating mazdutide, the world’s first approved GLP-1/GCG, is also the first to pit a drug from the class against semaglutide in a head-to-head comparison, the Suzhou-based drugmaker said in an Oct. 26 press release.

Novo markets its semaglutide as injectable Ozempic and oral Rybelsus for type 2 diabetes and as Wegovy for obesity.

Innovent pitted a 6-mg dose of mazdutide against a 1-mg semaglutide regimen in its study of 349 Chinese adults with early-stage type 2 diabetes (T2D) and obesity. To qualify for the China-only trial, patients had to have inadequate glycemic and weight control after lifestyle intervention, regardless of whether they were taking standard metformin monotherapy.

Mazdutide's performance against Novo's semaglutide allowed the trial to meet its primary endpoint, which looked at the proportion of patients who achieved hemoglobin A1C (HbA1C) or blood glucose levels over 7.0%, as well as body weight reduction of at least 10% from baseline at the study's 32-week mark. 

Some 48% of patients in the trial's mazdutide group met those blood sugar and weight loss benchmarks, compared to 21% in the semaglutide arm, Innovent said.

Mazdutide also had an apparent edge over semaglutide on both blood glucose levels and weight loss separately, helping patients lower their HbA1c by 2.03% and lose 10.26% of their weight from baseline on average. Semaglutide, meanwhile, triggered a 1.84% reduction in HbA1c levels and helped patients achieve an average 6% weight loss.

“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., explained in the release.

Mazdutide, approved in China for weight management and type 2 diabetes, may benefit “a wide range of patients requiring multifaceted 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., added. 

The drug won its first-in-class approval from China’s National Medical Products Administration (NMPA) in June, marking a breakthrough moment for incretin medicines. Targeting the GCG receptor can increase the body’s energy expenditure and improve hepatic fat metabolism, creating a powerful weight loss mechanism when added to the insulin benefits of GLP-1 agonists.

Innovent signed a 2019 agreement with Lilly to license the drug in China, marking an extension of a decade-long partnership between the two companies. Lilly maintains the rights to the mazdutide outside of China, where it has yet to win approval.

Mazdutide and semaglutide are also going head-to-head in another ongoing study that compares the medications in obesity accompanied metabolic-associated fatty liver disease. Innovent is planning to further study mazdutide in adolescents with obesity, metabolic dysfunction–associated steatohepatitis (MASH), certain heart failure indications and against Lilly’s tirzepatide in obesity.